肽载体的制作方法

专利名称：肽载体的制作方法
技术领域：
本发明涉及治疗组合物及其在治疗疾病中的应用。尤其是，本发明提供了治疗与 异常或不利的细胞增殖与迁移和/或生理作用有关的疾病的化合物、组合物以及方法。
背景技术：
大多数细胞毒药物由于对需要治疗的组织或细胞缺乏选择性而呈现出不利的毒
副作用。已经努力寻找各种方法以获得细胞毒药剂对靶细胞的选择性输送。 利用生物受体的配体作为药物载体将这些药物靶向输送到目标细胞中能减小
毒副作用并大大改进药物输送的效率。例如，围际专利公开号W097/19954公开了蒽环
霉素(anthracycline)细胞毒药剂如多柔比星(doxorubicin)与肽激素如LHRH、铃蟾肽
(bombesin)或生长抑素的偶联物。细胞毒药剂通过式_C(0)-(CH2)n-C(0)-， n = 0_7的连
接与肽共价结合。 与之类似，欧洲专利申请号EP1118336公开了生长抑素类似物，如奥曲肽 (octreotide)、兰瑞肽(lanreotide)和伐普月太(v即reotide)与细胞毒药物，如紫杉醇 (paclitaxel)、多柔比星(doxorubicin)或喜树碱(camptothecin)通过间隔基连接的结合 物，该间隔基具有结构-C(0)-(CH2)n-C(0)-， n = 0-7。 美国专利申请公开号2002/0115596公开了细胞毒药剂和寡肽的结合物，其中所 述寡肽的氨基酸序列是游离的前列腺特异性抗原优先断裂的序列。这样的结合物对于治疗 前列腺癌和良性前列腺肥大有利用价值。 美国专利申请公开号2003/0064984公开了 CC-1065和duocarmycins的细胞毒类 似物与可断裂的连接体以及靶向物质，如抗体或肽的结合物。细胞毒类似物通过连接体的 断裂而被释放出来。 国际专利申请号W002/34237公开了活性物质直接共价结合到多肽上的结合物。 据说该多肽能通过构象保护来稳定该活性物质，如在胃中的稳定性。 然而，仍然迫切需要靶向特异性、系统毒性和药代动力学特征得到改善的靶向细 胞毒药物。
发明概述 本发明提供了靶向细胞毒化合物，其包括结合在靶向部分上的细胞毒部分，所述
靶向部分为如生物受体的配体。该两部分通过连接体，如式I所示的连接体相结合 x-bH-b4-z (I)
其中
X是细胞毒物质或细胞抑制剂； B、B2，B3和B4各自独立地是(Doc)m， (A印a)n，-(C(0)-Al-A2-A3-A4-A5-C(0))s-或 (氨基酸)p， Al和A5各自独立地是CR力2 ; R1和R2各自独立地是H， F， Br， Cl， I， C(卜3。)烷基，C(2—30)烯基，取代的C(卜3。)烷 基，取代的C (2—30)烯基，SR3， S (0) R4或S (0) 2R5，或R1和R2共同形成C (3—30)环烷基，C (3—30)杂 环基或C(5—3。)芳环； R3， !^和RS各自独立地是Cd—3。)烷基，C(2—30)烯基，取代的Cd—3。)烷基，取代的 C (2—30)烯基； A2， A3和A4各自独立地是CR6R7， 0， S， (CH2) t或缺省; R6和R7各自独立地是H， F， Br， Cl， I， C(卜3。)烷基，C(2—30)烯基，取代的C(卜3。)烷
基，取代的C(2—3。)烯基，SR3， S(0)R4或S(0)2R5 ;或R6和R7共同形成环系;m独立地是0， 1， 2， 3， 4， 5， 6， 7， 8， 9或10 ; n独立地是0，l，2，3，4，5，6，7，8，9或10 ; p独立地是0，l或2; s独立地是1，2，3，4或5 ; t各自独立地是0，l，2或3 ; Z是生物受体的配体、其类似物或所述配体或所述类似物的衍生物；条件是 当X是多柔比星或多柔比星衍生物时，至少m和n之一不为0 ;且 当X是紫杉醇或紫杉醇衍生物时，B1是(氨基酸)p，其中p为1或2 ; 第一个优选的实施方式描述了式(I)的化合物，其中X是细胞毒部分。更优选，X
是蒽环霉素。再优选，X是喜树碱、喜树碱衍生物、紫杉醇、紫杉醇衍生物、多柔比星或多柔
比星衍生物；条件是当X是多柔比星或多柔比星衍生物时，至少m和n之一不为零，而当X
是紫杉醇或紫杉醇衍生物时，B1是(氨基酸)p，其中p为1或2 ; 所述第一个优选实施方式的进一步优选的实施方式中，所述发明描述了式(I)的 化合物，其中 X是喜树碱或喜树碱衍生物，其中所述喜树碱衍生物为
<formula>formula see original document page 131</formula>
或X是紫杉醇或紫杉醇衍生物，其中所述紫杉醇衍生物是
或X是多柔比星或多柔比星衍生物，其中所述多柔比星衍生物是
NH. 第二个优选的实施方式描述了式(I)的化合物，其中配体Z是生长抑素，铃蟾肽或 LHRH，或它们的类似物，或所述配体或所述类似物的衍生物。 在上述第二个优选实施方式的进一步优选实施方式中，本发明描述了式(I)的化 合物，其中Z是 下式的生长抑素类似物 -DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 ; -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr_NH2 ; -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 ; -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)-Thr_NH2 ; -Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr_NH2 ; -Caeg-cyclo (DCys-Pal-DTrp-Lys-DCys)-Thr(Bzl)_Tyr_NH2 ; -D2Nal-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Thr_NH2 ; -DPhe-cyclo[Cys-Phe-DTrp-Lys-Thr-Cys]-Thr-ol ; -cyclo({4_(-NH-C2H4-NH-C0-0)Pro}-Phg-DTrp-Lys-Tyr(4_Bzl)-Phe);或 -DPhe-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp_NH2 ; 或 它们的药学可接受盐； 或下式的LHRH类似物 Glp-His-Trp-Ser-Tyr-DLys(-)-Leu-Arg-Pro-Gly_NH2 ; Glp-His-Trp-S er-Tyr-DOrn(-)-Leu-Arg-Pro_Gly-NH2 ; Glp-His-Trp-Ser-Tyr-DDab(-)-Leu-Arg-Pro-Gly-NH2 ; Glp-His-Trp-Ser-Tyr-DDap(-)-Leu-Arg-Pro-Gly_NH2 ; Glp-His-Trp-Ser-Tyr-DApa(-)-Leu-Arg-Pro-Gly_NH2 ; Glp_Hi s-Trp-Ser-Tyr-DLys(-)-Leu—Arg-Pro—NHEt ;
Glp-Hi s-Trp-Ser-Tyr-DOrn (- Glp-His-Trp-Ser-Tyr-DDab(- Glp-Hi s-Trp-Ser-Tyr-DD即(- Glp-Hi s-Trp-Ser-Hi s_DLys(- Glp-Hi s-Trp-Ser-Hi s-DOrn(- Glp-Hi s-Trp-Ser-Hi s-DDab(- Glp-His-Trp-Ser-His-DDap(- — 一 它们的药学可接受盐； 或下式的铃蟾肽类似物 -Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 ; -Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2_NH) -Leu_NH2 ; -Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2_NH) -Phe_NH2 ; -Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 ; -Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 ; -Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 ; -Gln-Trp-Ala-Val-P Ala-His-Ala-Nle-NH2 ; -Gln-Trp-Ala-Val-P Ala-Ala-Phe-Nle-NH2 ; -Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 ; -Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2 ; -Gln-Trp-Ala-Val-Gly-His-Phe-Met-NH2 ; -DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 : -DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 : -DPhe-Gln-Trp-Ala-Val-P Ala-Ala-Phe-Nle-NH2 : -DPhe-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 : -DPhe-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 : -DPhe-Gln-Trp-Ala-Val-P Ala-His-Ala-Nle-NH2 : -DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 : -DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 : -DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2_NH) -DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2_NH) -DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2 ; -DPhe-Gln-Trp-Ala-Val-Gly-His-Phe-Met-NH2 ; -DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 ; 或它们的药学可接受盐。 第三个优选的实施方式描述了式(I)的化合物，其中，至少m和n之一不为O。 第四个优选的实施方式描述了尤其在本发明中公开结构的化合物。更优选的是本 发明实施例l-79所述的化合物和中间体。在优选的是实施例19-25， 28-32，40-42，45-65 和74-79所述的化合物。 第五个优选实施方式是下式化合物
Leu--Arg--Pro--NHEt ;
Leu--Arg--Pro--NHEt ;
Leu--Arg--Pro--NHEt ;
Trp--Tyr--Pro--Gly-NH2
Trp--Tyr--Pro--Gly-NH2
Trp--Tyr--Pro--Gly-NH2;或
Trp--Tyr--Pro--Gly-NH9;或
-Leu-NH2; -Phe-NH2;<formula>formula see original document page 134</formula><formula>formula see original document page 135</formula><formula>formula see original document page 136</formula><formula>formula see original document page 137</formula><formula>formula see original document page 138</formula><formula>formula see original document page 139</formula>
<formula>formula see original document page 140</formula>(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2
(Doc)4-A印a-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2
N-Suc-(Doc)3-A印a-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2
(Doc)4-A印a-Gaba-Gln-Trp-Ala-Val-pAla-His-Leu-Nle-NH2
,(Doc)4-A印a-Gaba-Gln-Trp墨Ala-Val-卩Ala-His-Leu-Nle-NH2
Olo.
C3
141
或它们的药学可接受盐。更优选的是下式化合物
<formula>formula see original document page 143</formula>
^^~(Doc)4-Aepa-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2 或它们的药学可接受盐。 在第六个优选的实施方式中，描述了选自表A中的化合物。
在第七个优选的实施方式中，描述了选自表B中的化合物。
在第八个优选的实施方式中，描述了选自表C中的化合物。
在第九个优选的实施方式中，描述了选自表D中的化合物。
在第十个优选的实施方式中，描述了选自表E中的化合物。
在第十一个优选的实施方式中，描述了选自表F中的化合物。
在第十二个优选的实施方式中，描述了选自表G中的化合物。
在第十三个优选的实施方式中，描述了选自表H中的化合物。
在第十四个优选的实施方式中，描述了选自表I中的化合物。 本发明第二个方案提供了一种药物组合物，其包括有效量的靶向细胞毒化合物或 其药学可接受盐和药学可接受载体，该靶向细胞毒化合物包括结合到靶向部分上的细胞毒 部分，该靶向部分可以是例如生物受体的配体。这两部分通过连接体相结合，该连接体为如 本发明的式I所定义。 本发明的第三个方案描述了为需要治疗的个体(subject)治疗疾病的方法，所述 方法包括给所述个体施用治疗有效量的式I的靶向细胞毒化合物或这些化合物的药学可 接受盐，其中所述疾病选自纤维化、良性前列腺增生、动脉硬化、再狭窄、乳腺癌、结肠癌、胰 腺癌、前列腺癌、肺癌、小细胞肺癌、卵巢癌、表皮癌和血癌。 本发明的第四个方案描述了为需要治疗的个体治疗疾病的方法，所述方法包括给 所述个体施用治疗有效量的式I的靶向细胞毒化合物或这些化合物的药学可接受盐，其中 所述疾病选自良性前列腺增生、再狭窄、乳腺癌、结肠癌、胰腺癌、前列腺癌、肺癌、小细胞肺 癌、卵巢癌、表皮癌和血癌。 本发明的第五个方案描述了为需要治疗的个体治疗疾病的方法，所述方法包括给 所述个体施用治疗有效量的式I的靶向细胞毒化合物或这些化合物的药学可接受盐，其中 所述疾病的特征是发生细胞的不良增生，所述的细胞表达一种或多种生长抑素型受体。
本发明的第六个方案描述了为需要治疗的个体治疗疾病的方法，所述方法包括给 所述个体施用治疗有效量的式I的靶向细胞毒化合物或这些化合物的药学可接受盐，其中 所述疾病的特征是发生细胞的不良增生，所述的细胞表达一种或多种铃蟾肽型受体。
本发明的第七个方案描述了为需要治疗的个体治疗疾病的方法，所述方法包括给 所述个体施用治疗有效量的式I的靶向细胞毒化合物或这些化合物的药学可接受盐，其中 所述疾病的特征是发生细胞的不良增生，所述的细胞表达一种或多种LHRH型受体。
除非另有说明，本发明中的术语"氨基酸"是指任何天然存在的氨基酸和非天然氨 基酸，其包括但不限于a -氨基酸、|3 -氨基酸、Y -氨基酸，可能是D-氨基酸或L-氨基酸。 除了N-末端氨基酸以外，所有氨基酸的縮写(如Ala)表示结构-NH-C(R) (R' )-CO-，其中， R和R'各自独立地是氢或氨基酸的侧链(如R二CHs和R' = H代表Ala)，或R和R'可
144连接形成环系。对于N-末端氨基酸，縮写代表结构(r2r3)-n-c(r)(r' )-co-，其中r2和r3
如式(I)所定义。 优选的氨基酸的示例如下，但不限于此Ala， Arg， Asp， Asn， Cys， Glu， pGlu， Gln， Gly， His， Ile， Leu， Lys， Met， Phe， Pro， Ser， Thr， Trp， Tyr， Val， P -Ala， Act， Apc， Gaba， Apn， Ahx， Ahp， Aoc， Anc， Adc， A皿，Ado， Acc， A3c， A4c， A5c， A6c， Aib， 0rn， Dab， Dap， hArg， 4Pal，3Pal，2Pal， Abu， Cha， Cit，Nle，Nva， Taz， 2Thi， 3Thi， Dhp， Dmt， 2Fua， 3Hyp， 4Hyp， Inc， I即，Ktp， hLeu. Oic， hPhe， Pip， Sar， Thz， Tic， Tle， Phg禾口 Caeg。 本发明化合物的肽部分也可以其它方式表示，如(Tyr11)生长抑素(l-14)-M^，其 中，在第一个括号内，天然序列有氨基酸被取代(如，Tyr"取代了生长抑素中的Phe11)。第 二个括号中的数字是指肽中的氨基酸数目(如，生长抑素(1-11)是指生长抑素的从第l到 第ll氨基酸的肽序列)。例如，(Tyr11)生长抑素(l-14)-NH2中的〃 NH2〃表示肽的C-末 端被酰胺化。(Tyr11)生长抑素(1-14)或(Tyr11)生长抑素(1-14)-OH表示C-末端是游离 酸。"烷基"是指含有一个或多个碳原子的烃基团，如果含有多个碳原子，则各碳原子 是通过单键相连。烷烃基团可以是直链或包含一个或多个支链或环基团。
〃取代的烷基〃 是指其中烃基团的一个或多个氢原子被一个或多个取代基所取 代的烷基，所述取代基选自卤素(即，氟，氯，溴和碘)，-OH， -CN， -SH， -NH2， -NHCH3， _N02， 被1-6个卤素取代的-(V2烷基，-CF3， -0CH3， -0CF3和_(CH2)。—4-C00H。不同的实施方式包 含了 1 ， 2 ， 3或4个取代基。-(CH2) 。—4-C00H的存在表明是烷基酸。包含有_ (CH2) 。—4_C00H或 由_(CH2)。—厂COOH构成的烷基酸的实例包括2-降莰烷乙酸，叔丁酸和3-环戊基丙酸。
"杂烷基"是指烃基中的一个或多个碳原子被一个或多个下述基团所取代的烷基 氨基，酰氨基，-O-或羰基。不同的实施方式包含了 l或2个杂原子。 〃取代的杂烷基〃 是指其中烃基团的一个或多个氢原子被一个或多个取代基所 取代的烷基，所述取代基选自卤素(即，氟，氯，溴和碘)，-OH， -CN， -SH， -NH2， -NHCH3， _N02， 被1-6个卤素取代的-(V2烷基，-CF3， -0CH3， -0CF3和_(CH2)。—4-C00H。不同的实施方式包 含了 1，2，3或4个取代基。"烯基"是指由两个或多个碳原子组成的含有一个或多个碳碳双键的烃基团。烯基 可以是直链或包含一个或多个支链或环基团。 〃取代的烯基〃 是指烯基中的一个或多个氢原子被一个或多个取代基所取代， 所述取代基选自卤素(即，氟，氯，溴和碘)，-OH， -CN， -SH， -NH2， -NHCH3， _N02，被1-6个卤素 取代的-C卜2烷基，_CF3， -0CH3， -0CF3和_(CH2)。—4-C00H。不同的实施方式包含了 1， 2， 3或4 个取代基。 〃芳基〃 是指任选取代的芳香基团，该芳香基团具有至少一个含共轭_电子体 系的环，含有至多为两个共轭或稠合的环系。芳基包括碳环芳基，杂环芳基和联芳基。优选 地，芳基为5或6元环。杂环芳基中优选的原子是一个或多个硫，氧和/或氮。芳基的实例 包括苯基，1-萘基，2-萘基，喷哚，喹啉，2-咪唑和9-蒽。芳基的取代基选自-(V4烷基，-(V4 烷氧基，卤素(即，氟，氯，溴和碘)，-oh， -cn， -sh， -nh2， -n02，被1_5个卤素取代的-c卜2烷 基，-CF3， -0CF3和_(CH2)。—4-C00H。不同实施方式中的芳基包含了 0， 1，2，3或4个取代基。
"芳烷基"是指"烷基"与"芳基"相连接。
环烷基包括碳原子数为本领域公知的单环烷基或双环烷基。 杂环包括含有一个或多个如氧，氮和/或硫的杂原子的单环和双环体系。环体系 可以是芳香性的，如吡啶，吲哚，喹啉，嘧啶，噻吩，呋喃，苯并噻吩，四唑，二氢吲哚，吲唑， N-甲酸基喷哚，苯并咪唑，噻唑和噻二唑。环体系还可以是非芳香性的，如吡咯烷，哌啶，吗 啉等。 普通化学技术人员能看出本发明所列出的含有杂原子取代基的某些组合所定义 的化合物会在生理条件下缺乏稳定性。因此，这样的化合物不是优选化合物。
Doc是8-氨基-3，6-二氧辛酸，由下列结构表示
<formula>formula see original document page 146</formula>A印a是4-(2_氨基乙基)-1-羧基甲基_哌嗪，由下列结构表示
:0146] :0147]
Sue或succ是琥珀酰，有下列结构表示
:0148] :0149]
Glut或戊二酰基具有下列结构
:0150] :0151]
喜树碱部分具有以下结构
:0152] :0153]
喜树碱衍生物部分包括但不限于<formula>formula see original document page 147</formula><formula>formula see original document page 148</formula>
多柔比星部分具有下列结构<formula>formula see original document page 149</formula>
多柔比星衍生物部分包括但不限于
DLys(-)有下列结构表示
<formula>formula see original document page 149</formula> D0rn(-)由下列结构表示
<formula>formula see original document page 149</formula>
DDab(-)由下列结构表示
<formula>formula see original document page 149</formula> DDap(-)由下列结构表示
<formula>formula see original document page 150</formula>
MY
<formula>formula see original document page 150</formula>DApa(-)由下列结构表示本发明的某些縮写定义如下
Abua-氨基丁酸Acci-氨基-i-环(c3-c9)烷基羧酸A3cl-氨基-l-环丙烷羧酸A4cl-氨基-l-环丁烷羧酸A5cl-氨基-l-环戊烷羧酸A6cl-氨基-l-环己烷羧酸Act4_氨基_4-羧基四氢吡喃，由下式表示<formula>formula see original document page 150</formula> Aib a-氨基异丁酸 Ala或A丙氨酸 P-Ala P-丙氨酸 Ape 表示结构


Arg或R精氨酸 hArg 高精氨酸 Asn或N天冬酰氨酸


<formula>formula see original document page 152</formula>
Ser或
肌氨酸或N-甲基氨基乙酸 S丝氨酸
|3 -(4_噻唑基)丙氨酸，由下式结构表示 2Thi|3 _ (2-噻吩基)丙氨酸 3Thi|3 _ (3-噻吩基)丙氨酸 Thr或T苏氨酸 Thz 噻唑烷-4-羧酸 Tic 1，2，3，4_四氢异喹啉-3-羧酸 Tie 叔_亮氨酸 Trp或W色氨酸 Tyr或Y酪氨酸 Val或V缬氨酸 Gaba 4_氨基丁酸 Apn 5_氨基戊酸 Ahx 6-氨基己酸 Ahp 7-氨基庚酸 Aoc 8-氨基辛酸 Anc 9_氨基壬酸 Adc 10-氨基癸酸 Aun ll-氨基i^一酸 Ado 12-氨基十二酸 Phg 苯基甘氨酸 Caeg N_(2_氨基乙基)_N_(2-胞嘧啶基_1_氧代_乙基)_甘氨酸，由下式结构
表示
<formula>formula see original document page 152</formula>
本发明所用的其它縮写定义如下 Aloe:烯丙氧羰基
Boc :叔丁氧羰基Bhoc二苯甲氧羰基Bzl :苄基DCM :二氯甲烷Dde :l-(4，4-二甲基-2，6-二氧环己-l-基亚基)乙基]DIC :N， N- 二异丙基碳二亚胺DIEA :二异丙基乙基胺Dmab :4- {N- (1- (4， 4- 二甲基-2， 6- 二氧环己基亚基)-3-甲基丁基)_氨基}
苄基DMAP :4-(二甲基氨基)吡啶DMF :二甲基甲酰胺DNP :2，4-二硝基苯Et :乙基Pmoc :芴基甲氧羰基HBTU :2- (1H-苯并三唑-1-基)-1 ， 1 ， 3， 3-四甲基脲鎗六氟磷酸酯clfex环己基HOAT :0- (7-氮杂苯并三唑-1-基)-1 ， 1 ， 3， 3-四甲基脲鎗六氟磷酸酯HOBt :1-羟基-苯并三唑Mmt :4-甲氧基三苯甲基證N-甲基吡咯烷酮Pbf :2， 2， 4， 6， 7-五甲基二氢苯并呋喃_5-磺酰基tBu :叔丁基TIS :三异丙基硅烷TOS :甲苯磺酰基trt :三苯甲基TFA :三氟醋酸TFFH :四甲基氟甲脒鎗六氟磷酸酯(tetramethylfluoroforamidini咖hexaflu
orophos,phate)Z :苄氧羰基发明详述
本发明描述了靶向细胞毒化合物以及治疗肿瘤、增生和其它与细胞不良增生有关的病症的方法。该靶向细胞毒化合物包括结合到靶向部分上的细胞毒部分，其中靶向部分
为，如生物受体的配体。 利于用于本发明的生长抑素肽的实例将在此进行描述。进一步的实施例是公式或
下述引用的公开专利申请中涵盖的化合物，这些申请在本发明中被全文引用 PCT申请号W0 03/057214(2003) 美国申请号20030191134(2003) 美国申请号20030083241 (2003) 美国专利号6， 316， 414(2001)
153
PCT申请号WO 02/10215(2002) PCT申请号WO 99/22735(1999) PCT申请号WO 98/08100(1998) PCT申请号WO 98/44921(1998) PCT中请号WO 98/45285 (1998)PCT申请号WO 98/44922(1998) 欧洲中请号P5 164 EU(发明人G. Keri); Van Binst， G. et al. P印tide Research 5:8(1992); Horvath， A. et al. Abstract, 〃 Conformations of Somatostatin Analogs HavingAntitumor Activity" ，22nd European peptide Symposium, September 13-19， 1992， Interlaken， Switzerland ;PCT申请号W091/09056(1991)
欧洲申请号0363589 A2(199Q)
美国专利号4，904，642(1990)美国专利号4，871，717(1989)美国专利号4，853，371(1989)美国专利号4，725，577(1988)美国专利号4，684，620(1987)美国专利号4，650，787(1987)美国专利号4，603，120(1986)美国专利号4，585，755(1986)欧洲申请号0203031A2(1986)美国专利号4，522，813(1985)美国专利号4，486，415(1984)美国专利号4，485，101(1984)美国专利号4，435，385(1984)美国专利号4，395，403(1983)美国专利号4，369，179(1983)美国专利号4，360，516(1982)美国专利号4，358，439(1982)美国专利号4，328，214(1982)美国专利号4，316，890(1982)美国专利号4，310，518(1982)美国专利号4，291，022(1981)美国专利号4，238，481(1980)美国专利号4，235，886(1980)美国专利号4，224，199(1980)美国专利号4，211，693(1980)美国专利号4，190，648(1980)
美国专利号4，146，612(1979)美国专利号4，133，782(1979)美国专利号5，506，339(1996)美国专利号4，261，885(1981)美国专利号4，728，638(1988)美国专利号4，282，143(1981)美国专利号4，215，039(1980)美国专利号4，209，426(1980)美国专利号4，190，575(1980)欧洲专利号o:〗891〖;0(1990); 欧洲申请号0505680(1982); 欧洲申请号0083305(1982); 欧洲申请号0030920(1980); PCT申请号W088/05052(1988); PCT申请号W090/12811(1990); PCT申请号W097/01579(1997); PCT申请号W091/18016(1991); 英国申请号GB2， 095， 261 (1981);禾口 法国申请号FR2， 522， 655(1983)。 利于用于本发明的LHRH(黄体生成素释放激素)肽的实例将在此进行描述。进一 步的实施例是公式或下述引用的公开专利申请中涵盖的化合物，这些申请在本发明中被全 文引用 欧洲申请号0081877 (1983) 欧洲申请号0328089 (1989) 欧洲申请号0417454 (1991) 欧洲申请号0626170 (1994) 欧洲申请号0832107 (1998) 欧洲申请号1340768(2003) 美国申请号2003040482 (2003) 美国专利号4， 317， 815(1982) 美国专利号4，431，635(1984) 美国专利号4， 581， 169 (1986) 美国专利号4，628，044(1986) 美国专利号4， 642， 332 (1987) 美国专利号4， 656， 247 (1987) 美国专利号4， 721， 775 (1988) 美国专利号5， 075， 224(1991) 美国专利号5， 140， 009 (1992) 美国专利号5， 484， 592 (1996)
H-Lys(Boc)-DTyr(tBu)-DTyr(tBu)-Cys(Trt)-Tyr(tBu)-DTrp(Boc)-Lys(Boc)-Abu-Cys (Trt)-Thr (tBu)-Rink Amide MBHA树脂 标题的保护的肽-树脂是利用应用生物系统公司(A卯lied Biosystems (ABI)(Foster City， CA))模型433A的肽合成仪，采用芴甲氧羰基(Fmoc)化学保护方法自动合成的。Rink Amide MBHA(4-甲基二苯甲基胺)树月旨(Novabiochem， SanDiego， CA)具有可利用的0.72 mmol/g的取代。利用了下述的Fmoc氨基酸(AnaSpec， San Jose，CA) :Fmoc_Thr(tBu)_0H， Fmoc-Cys(Trt)_0H， Fmoc-Lys(Boc)_0H， Fmoc-DTrp(Boc)_0H，Fmoc-Tyr (tBu)_0H， Fmoc-DTyr (tBu)_0H， Fmoc_Phe_0H， Fmoc-Cys(Trt)_0H，Fmoc-Thr (tBu) -OH禾P Fmoc-Abu-0H。以0. 25 mmol规模进行合成。用含20%哌啶的N_甲基吡咯烷酮(NMP)处理30分钟去除Fmoc基团。在各偶联步骤中，首先将Fmoc氨基酸(4 eq，1,1)在含有0.45M 2-(l-H-苯并三唑-l-基)-l，l，2，3-四甲基脲鎗六氟磷酸酯(HBTU)和0. 45Ml-羟基-苯并三唑(H0BT)的2mlN， N-二甲基甲酰胺(DMF)溶液中预活化。将得到的活化氨基酸酯、lmL二异丙基乙基胺(DIEA)和lmLNMP加到树脂中。设定ABI 433A肽合成仪的程序进行下列反应循环(1)用NMP清洗，(2)用含20%哌啶的NMP溶液处理30分钟，去除Fmoc保护基，(3)用NMP清洗，(4)用预先活化的Fmoc氨基酸偶联1个小时。根据序列逐个偶联到树脂上。肽链偶联完毕后，去除Fmoc，用DMF和二氯甲烷(DCM)彻底清洗树脂。 实施例2 H-Doc-Doc-Doc-Doc-Lys(Boc)-DTyr(tBu)-DTyr(tBu)-Cys(Trt)-Tyr(tBu)-DTrp(Boc)-Lys (Boc)-Abu-Cys (Trt)-Thr (tBu)-Rink Amide MBHA树脂 基本按照实施例1的方法合成标题的保护的肽_树脂。Fmoc-8-氨基_3， 6_ 二氧辛酸(Fmoc_Doc_0H)购自Chem-Impex Intematoinal, Wood Dale, IL。 H-Lys (Boc)-DTyr (tBu)-DTyr(tBu)_Cys(Trt)_Tyr(tBu)-DTrp(Boc)_Lys(Boc)-Abu-Cys(Trt)_Thr(tBu)_Rink Amide MBHA树脂(0. 45 mmol的规模)合成完毕后，将保护的肽_树脂转至振荡器上的反应瓶中，进行人工分析。树脂在含有Fmoc-Doc-OH(l. 5 eq，O. 75 mmol) 、N，N_ 二异丙基碳二酰亚胺(DIC，1.5 eq，0.75mmo1)和H0BT(1.5 eq，0.75 mmol)的DMF溶液中振摇2个小时。用DMF清洗，然后用含20 %哌啶的DMF溶液去除Fmoc保护基。用人工操作的相同方法，将其余三个Doc残基相继偶联到树脂上。用含20%哌啶的DMF溶液去除Fmoc保护基后，再用DMF和DCM清洗保护的肽-树脂。
实施例3 H-Doc-Doc-Doc-Doc-Doc-Doc-Lys(Boc)-DTyr(tBu)-DTyr(tBu)-Cys(Trt)-Tyr(tBu) -DTrp (Boc) -Lys (Boc) —Abu—Cys (Trt) -Thr (tBu) -Rink Amide MBHA树月旨
基本按照实施例2所述的合成方法合成标题的保护的肽_树脂。
实施例4 H-A印a-Lys (Boc) -DTyr (tBu) -DTyr (tBu) -Cys (Trt) -Tyr (tBu) -DTrp (Boc) -Lys (Boc)-Abu-Cys (Trt)-Thr (tBu)-Rink Amide MBHA树脂 基本按照实施例1所述的方法合成标题的保护的肽_树脂。Fmoc-4-(2-氨基乙基)_1_羧甲基_哌嗪(Fmoc-A印a-0H)购自Neosystem， Strasbourg, France。 H-Lys (Boc)-DTyr(tBu)-DTyr(tBu)-Cys(Trt)-Tyr(tBu)-DTrp(Boc)-Lys(Boc)-Abu—Cys(Trt)-Thr(tBu)-Rink Amide MBH树脂偶联完毕后，将保护的肽-树脂转至振荡器上的反应瓶中，进行人工分析。用含有0-(7-氮杂苯并三唑-l-基)-l，l，3，3-四甲基脲鎗六氟磷酸酯(HATU，1. 4 eq，O. 7,1)和1_羟基_7_氮杂苯并三唑(HOAT， 1. 4 eq. ，0. 7,1)的2mL DMF溶液预活化Fmoc-A印a-OH(l. 5eq，0. 75mmol)达2分钟。将所得活化的Fmoc-A印a-OH的酯和lmLDIEA加至反应瓶中，振摇该混合物2个小时。用DMF清洗树脂，并用含20%哌啶的DMF溶液去除Fmoc保护基。用DMF和DCM清洗保护的肽-树脂。
实施例5 H-Doc-Doc-Doc-Doc-A印a-Lys (Boc) -DTyr (tBu) -DTyr (tBu) -Cys (Trt) -Tyr (tBu)
-DTrp (Boc) -Lys (Boc) —Abu—Cys (Trt) -Thr (tBu) -Rink Amide MBHA树月旨 基本按照实施例4所述的方法合成标题的保护的肽_树脂。按照实施例2描述的
相应方法偶联Fmoc-Doc-OH。 实施例6 H-DPhe-Cys(Trt)-Tyr(tBu)-DTrp(Boc)-Lys(Boc)-Abu-Cys(Trt)-Thr(tBu)-RinkAmide MBHA树脂 基本按照实施例1所述的方法合成标题的保护的肽_树脂。Fmoc-DPhe-OH购自AnaSpec， San Jose， CA。
实施例7 H-A印a-DPhe-Cys (Trt) -Tyr (tBu) -DTrp (Boc) -Lys (Boc) -Abu-Cys (Trt) -Thr (tBu)-RinkAmide MBHA树脂 基本按照实施例4所述的方法合成标题的保护的肽_树脂。
实施例8 5-0-tBoc-甘氨酰-5- (R)-乙基-9， 10- 二氟_1 ， 4， 5， 13-四氢_3H， 15H_氧杂卓并中氮茚并[l，2-b]喹啉-3，15-二酮 将5- (R)-乙基-9， 10- 二氟-1 ， 4， 5， 13-四氢_5_羟基_3H， 15H-氧杂卓并[3， ， 4，:6， 7]中氮茚并[l，2-b]喹啉-3，15-二酮(300mg) 、Boc-Gly-0H(923 mg，7eq.)禾P4-(二甲基氨基)吡啶(DMAP) (560. 4mg，6eq.)溶于DCM和DMF(30 mL，v/v，30/0. 5)的混合溶剂中。然后，加入1- (3- 二甲氨基丙基)-3-乙基碳二酰亚胺(EDC) (1. 08g， 7. 5eq.)。室温下，搅拌混合物过夜，减压除去溶剂。将残余物溶于100mLDCM中，相继用10%柠檬酸水溶液(20mLX2)、饱和NaHC03溶液(20mLX2)和饱和盐水(10mLX3)洗涤。有机层用MgS04干燥，过滤、减压蒸发去除溶剂。用硅胶柱快速色谱纯化粗产物，流动相为含10X甲醇的DCM，得到纯品5-0-tBoc-甘酰胺-5-(R)-乙基_9，10-二氟-1，4，5，13-四氢_3H， 15H-氧杂卓并[3'，4':6，7]中氮茚并[l，2-b]喹啉-3，15-二酮330mg，TLC(硅胶，DCM/MeOH:9/1) :Rf = 0. 43。电喷雾离子质谱(ESI MS)分析得到分子量为556. 4(与计算的分子量555. 5相符)。
实施例9 5-0-甘氨酰-5-(R)-乙基_9，10-二氟-1，4，5，13-四氢_3H， 15H-氧杂卓并[3'，4' :6， 7]中氮茚并[l，2_b]喹啉-3，15-二酮三氟乙酸盐
<formula>formula see original document page 159</formula> 在氮气氛围下，用30%三氟乙酸(TFA)的DCM溶液处理5_0_叔丁基-甘氨 酰-5-(R)-乙基_9，10-二氟-1，4，5，13-四氢-3H，15H-氧杂卓并[3'，4' :6，7]中氮茚并 [l，2-b]喹啉-3，15-二酮(330mg)l个小时。减压下，除去TFA和溶剂。加冷乙醚研磨残余 物，得到微黄色粉末。TLC(硅胶，DCM/MeOH:9/1) :Rf = 0. 13。 ESI MS分析得到的分子量为 456. 0 (与计算的分子量455. 4相符)。
实施例10 5-0- (N-戊二酰_甘氨酰)-5- (R)-乙基_9， 10- 二氟_1 ， 4， 5， 13-四氢_3H， 15H-氧 杂卓并[3'，4' :6，7]中氮茚并[1，2-b]喹啉-3，15-二酮
<formula>formula see original document page 159</formula>
将5-0-甘氨酰-5-(R)-乙基_9， 10-二氟_1， 4， 5， 13-四氢_3H， 15H-氧杂卓并 [3'，4' :6，7]中氮茚并[1，2-b]喹啉-3，15-二酮(208mg，0. 37mmo1)、戊二酸酐(66mg， 0. 58,1， 1. 5eq.)和三乙胺(243mL)混合物的DMF(7mL)溶液在室温下搅拌3个小时。减 压蒸除溶剂。残余物溶于水(lOmL)中，(TC下，加入O. 5N HC1调节溶液的pH值至3。将产 生的沉淀滤出，用冷水和醚洗涤。减压干燥，得到固体160mg。收率为77%。 ESI MS分析得 出分子量为570. 0(与计算出的分子量569. 5相符)。HPLC分析的纯度为98%。
实施例11 5-0- (N-琥珀酰_甘氨酰)-5- (R)-乙基_9， 10- 二氟_1 ， 4， 5， 13-四氢_3H， 15H-氧 杂卓并[3'，4' :6，7]中氮茚并[1，2-b]喹啉-3，15-二酮
<formula>formula see original document page 159</formula> 基本按照实施例10的方法，利用琥珀酸酐合成标题化合物。收率为86%。 ESI MS 分析得出分子量为556. 2(与计算的分子量555. 50相符)。HPLC分析的纯度为96%。
实施例12 喜树碱-20- (S) -

<formula>formula see original document page 159</formula>
将喜树碱(0. 79 g，2. 2 ,1) 、Boc-Gly-0H(1. 2 g，6. 8mmol，3eq.)禾PDMAP(O. 83g，6. 8mmol，3eq.)溶于DCM和THF的混合溶剂(18mL， v/v，5/l)中。在冰水浴中冷却该混合 物。然后加入l，3-二异丙基碳二酰亚氨(DIC) (1. lmL，6. 8,1， 3. leq. ) ， (TC下搅拌0. 5个 小时，将混合物升温至室温，然后搅拌过夜。用50mLDCM稀释该溶液，然后相继用10%拧檬 酸水溶液(20 mL x 2)、饱和NaHC03(20mLX2)和饱和盐水(10mLX3)洗涤。有机层用MgS04 干燥，过滤，滤液减压浓縮。得到粗产物，用硅胶快速分离色谱纯化，流动相为含4%甲醇的 DCM，纯化得纯品喜树碱-20- (S) - (O-tBoc-甘氨酰)(1. 07 g，白色固体)。TLC (硅胶，DCM/ MeOH :9/1) :Rf = 0. 6。 MS ESI分析得出的分子量为506. 3 (与计算的分子量505. 53相符)。
实施例13 喜树碱-20-(S)_(0-甘氨酰)三氟乙酸盐
氮气氛围下，用含50 % TFA的DCM处理喜树碱-20- (S) -
(1. 07g，2. lmmol)达1个小时。减压除去TFA和溶剂。用冷乙醚研磨残余物，形成沉淀，过 滤，用冷乙醚洗涤固体，得到微黄色粉末(0.9 g，1.78 mmol)。收率为83X，TLC(硅胶，DCM/ MeOH :9/1) :Rf = 0. 23。 ESI MS分析得出分子量为406. 2 (与计算的分子量405. 41相符)。
实施例14 喜树碱-20- (S) -

在室温下搅拌喜树碱_20-(S)-(0-甘氨酰)三氟乙酸盐(0. 9 g， 1. 7mmo1)，琥珀 酸酐(0. 35g，3. 5mmol，2eq.)和三乙胺(0. 72mL，3eq.)在DMF(10mL)中的混合物达5分钟。 过滤、收集生成的沉淀。将收集到的固体悬浮于冷水(10mL)中。加入5%柠檬酸水溶液调 节水悬浮液的pH值至2。 (TC下搅拌0.5小时，滤出沉淀，用冷水和醚洗涤沉淀，减压干燥固 体，得到产物O. 88 g(1.58 mmol)。收率为99%。 ESI MS分析的分子量为505. 7 (与计算出 的分子量505. 49相符)。HPLC分析的纯度为99% 。
实施例1 5 喜树碱-20- (S) -

<formula>formula see original document page 160</formula> 用戊二酸酐基本按照实施例14所述的方法合成标题化合物。收率为75%。 ESI MS分析的分子量为520. 5 (与计算的分子量519. 52相符)。HPLC分析的纯度为98% 。
实施例16 喜树碱-20- (S) -

0 °C下，在喜树碱(350mg)禾P DMAP(180mg)的DCM(10mL)的溶液中加入 Boc-Val-F(2eq.)的DCM溶液，Boc-Val-F是采用文献记载的方法(Carpino etal. ，J. Org. Chem. ，56,2611,1991)制备的。0-5。C下搅拌30分钟，将混合物升温至室温，并连续搅拌过 夜。用氯仿(30mL)稀释混合物，用水、10X柠檬酸水溶液和饱和的NaHC03洗涤，用MgS04干 燥，然后过滤。减压除去溶剂后，在硅胶柱上纯化残余物，流动相为氯仿/丙酮(9 : 1)。将 含有目标产物的各部分洗脱液收集起来，然后减压浓縮得到固体。
实施例17 喜树碱-20- (S) - (0-缬氨酰基)三氟乙酸盐
用含35 % TFA的氯仿(10mL)溶液处理实施例16所制得的喜树 碱-20-(S)-
达30分钟。减压除去TFA和溶剂，得到固体。ESIMS分 析的分子量为448. 4(与计算的分子量447. 50相符)。
实施例18 喜树碱-20- (S) -

向含有喜树碱_20-(S)-(0-缬氨酰)三氟乙酸盐(150mg)、琥珀酸酐(4eq.)和 DMAP(2eq.)的氯仿(10mL)的混合溶液中加入三乙胺(6eq.)。室温搅拌过夜，用氯仿(20mL) 稀释反应混合物。用水和柠檬酸水溶液洗涤稀释后的溶液，MgS(^干燥，过滤。减压除去 溶剂，加入丙酮研磨残余物成粉状。得到120mg的标题化合物。TLC(硅胶，氯仿/甲醇= 9 : 1) :Rf = 0. 22。 ESI MS分析的分子量为548. 2 (与计算的分子量547. 57相符)。 [CHSO] 实施例19 {5-(R)_乙基-9，10-二氟-1，4，5，13-四氢_3H， 15H-氧杂卓并[3'，4' :6，7]中 氮茚并[1 ， 2-b]喹啉-3， 15- 二酮-5-0-甘氨酰-谷二酰} - (Doc) 6-Lys-DTyr-DTyr-cyclo ( Cys_Tyr_DTrp_Lys_Abu_Cys_)_Thr_NH2
将实施例3的H- (Doc) 6_Lys (Boc) -DTyr (tBu) -DTyr (tBu) -Cys (Trt) -Tyr (tBu) _D Trp (Boc)-Lys (Boc)-Abu-Cys (Trt)-Thr (tBu)-Rink Amide MBHA树月旨(0. 196,1)与实施
<formula>formula see original document page 161</formula>
(Doc)6-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH,例10的5-0- (N-戊二酰-甘氨酰)-5- (R)-乙基-9， 10- 二氟-1 ， 4， 5， 13-四氢_3H， 15H-氧 杂卓并[3'，4' :6， 7]中氮茚并[l，2-b]喹啉-3，15-二酮(0. 123 g， 0. 22mmol， 1. leq.)和 DlC(136ii L，O. 88mmol，4. 4 eq.)以及1_羟基_7_氮杂苯并三唑(HOAT) (30mg， 0. 22,1， 1. leq.)混合到5mL DCM中。振摇混合物2天。相继用DMF、甲醇和DCM清洗树脂。在空气 中干燥后，用TFA、H^和三异丙基硅烷(TIS) (9. 5mL/0. 85mL/0. 8mL)的混合物处理树脂2个 小时。过滤除去树脂，将滤液倒入100mL冷醚中。离心，收集沉淀物。将粗产物溶于100mL 的5% AcOH水溶液中，然后向其中逐滴加入碘甲醇溶液，直至溶液保持为黄色。再搅拌反应 液1个小时。加入10% Na2S203水溶液淬灭过量的碘。用制备HPLC系统纯化溶液中的粗产 物，使用的色谱柱为4X43cm的C18DYNAMAX-100A°(Varian， Walnut Creek， CA)。从80% A 和20% B至55X A和45% B线性梯度洗脱色谱柱50分钟，其中A为含O. 1% TFA的水溶 液，B为含0. 1 % TFA的丙腈溶液。通过分析HPLC检测各部分洗脱液成分。收集含有纯净 产物的洗脱液，冻干，收率为25% 。分析型HPLC分析的纯度为99. 9% 。 ESI MS分析的分子 量为2761. 1 (与计算的分子量2761. 04相符)。
实施例20 {5_(R)_乙基-9， 10-二氟_1，4，5， 13-四氢_3H， 15H_氧杂卓并[3'，4' :6，7]中 氮茚并[1 ， 2-b]喹啉-3， 15- 二酮-5-0-甘氨酰-戊二酰} - (Doc) 4-Lys-DTyr-DTyr-cyclo ( Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
(Doc)(Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH: 基本按照实施例19所述的方法合成，利用实施例2的H-Doc-Doc-Doc-Doc-Lys (B oc)-DTyr (tBu)-DTyr (tBu)-Cys (Trt)-Tyr(tBu)-DTrp(Boc)-Lys(Boc)-Abu-Cys(Trt)-Thr (tBu)-Rink Amide MBHA树脂合成标题化合物。收率为2 1.4%。分析型HPLC分析的纯度 为99. 9%。 ESI MS分析的分子量为2471. 2(与计算的分子量2471. 727相符)。
实施例21 {5_(R)_乙基-9， 10-二氟_1，4，5， 13-四氢_3H， 15H_氧杂卓并[3'，4' :6，7]中 氮茚并[1， 2-b]喹啉-3， 15- 二酮-5-0-甘氨酰-琥珀酰} -A印a-DPhe-cyclo (Cys-Tyr-DTr p-Lys-Abu-Cys)_Thr_NH2
Aepa-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2 基本按照实施例19所述的方法合成，利用实施例11的5-0_(N-琥珀酰-甘氨 酰)-5-(R)-乙基_9，10-二氟-1，4，5，13-四氢-3H，15H-氧杂卓并[3'，4' :6，7]中氮茚 并[l，2-b]喹啉_3， 15-二酮和实施例7的H-A印a-DPhe-Cys (Trt)-Tyr (tBu)-DTrp (Boc) -Lys (Boc)-Abu-Cys (Trt)-Thr (tBu)-Rink Amide MBHA Resin合成标题化合物。收率为 48%。分析型HPLC分析的纯度为99.9X。 ESI MS分析的分子量为1739. 8 (与计算的分子 量1740. 14相符)。
实施例22 喜树碱-20- (S) -0-甘氨酰_琥珀酰-Doc-Doc-Doc-Doc-A印a-DPhe-cyclo (Cys-Ty
r_DTrp_Lys_Abu_Cys)_Thr_NH2
(Doc)4-Aepa-DPhe-cycto(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2 基本按照实施例19的方法，利用实施例14的喜树碱-20-(S)-
禾口 H-Doc-Doc-Doc-Doc-A印a-DPhe-Cys (Trt) -Tyr (tBu) -DTrp (Boc) -Lys (Boc) -Abu -Cys (Trt)-Thr (tBu)-Rink Amide MBHA树脂合成标题化合物。收率为32%。分析型HPLC 分析的纯度为99. 9%。 ESI MS分析的分子量为2269. 0(与计算的分子量2269. 8相符)。
实施例23 喜树碱-20- (S) -0-甘氨酰_戊二酰-A印a-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-
Lys-Abu-Cys)_Thr_NH2
Aepa-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2 基本按照实施例19的方法，利用实施例15的喜树碱-20-(S)-
和实施例4的H-A印a-Lys (Boc) -DTyr (tBu) -DTyr (tBu) -Cys (Trt) -Tyr (tBu) -DTrp (B oc) -Lys (Boc) -Abu-Cys (Trt) -Thr (tBu) -Rink Amide MBHA树脂，合成标题化合物。收率为 11%。分析型HPLC分析的纯度为95X。 ESI MS分析的分子量为2008.9(与计算的分子量 2009. 2相符)。
实施例24 喜树碱-20- (S) -0-缬氨酰_琥珀酰-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _T
hr-NH2
DPhe"Cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2 基本按照实施例19的方法，利用实施例18的喜树碱-20- (S) -
和实施例6的H-DPhe-Cys (Trt) -Tyr (tBu) -DTrp (Boc) -Lys (Boc) -Abu-Cys (Trt) _T hr (tBu)-Rink Amide MBHA树脂合成标题化合物。得到145mg乳白色固体。ESI MS分析的 分子量为1562. 4(与计算的分子量1561. 8相符)。
实施例25 {5_(R)_乙基-9， 10-二氟_1，4，5， 13-四氢_3H， 15H_氧杂卓并[3'，4' :6，7]中 氮茚并[1， 2-b]喹啉-3， 15- 二酮-5-0-甘氨酰-琥珀酰} -DPhe-cyclo (Cys-Tyr-DTrp-Lys -Abu-Cys)-Thr-NH2
DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH 基本按照实施例19的方法，利用实施例11的{5_(R)_乙基-9，10-二氟-1，4，5， 13-四氢-3H，15H-氧杂卓并[3'，4':6，7]中氮茚并[l，2_b]喹啉-3， 15-二酮-5-0-(N_甘 氨酰_琥珀酰)和实施例6的H-DPhe-Cys (Trt) -Tyr (tBu) -DTrp (Boc) -Lys (Boc) -Abu-Cys (Trt)-Thr (tBu)-Rink Amide MBHA树脂合成标题化合物。得到乳白色固体。ESI MS分析 的分子量为1570. 2 (与计算的分子量1569. 72相符)。
实施例26 H-A印a- (Doc) 4_Gln (Trt) _Trp (Boc) _Ala_Val_ P Ala_His (Trt) _Leu_Leu_Rink AmideMBHA树脂 基本按照实施例5的方法合成标题保护的肽-树脂。Fmoc-Hi s (Trt) _0H， Fmoc-Gln (Trt) _0H， Fmoc_Leu_0H， Fmoc_Ala_0H禾口 Fmoc- P Ala-0H购自AnaSpec (San Jose， CA)。 实施例27 H-A印a- (Doc) 4_DPhe_Gln (Trt) _Trp (Boc) _Ala_Val_ P Ala-His (Trt_Leu_Leu_Ri nk Amide MBHA树脂 基本按照实施例26的方法合成标题保护的肽_树脂。
实施例28 喜树碱-20- (S) -0-甘氨酰_琥珀酰-A印a- (Doc) 4-Gln-Trp-Ala_Val- P Ala-His_
Leu_Leu_NH2 室温下，将DCM(7mL)和DMF(7mL)中的实施例26的H-A印a-(Doc)4_Gln(Tr t)-Trp (Boc)-Ala-Val-PAla-His(Trt)-Leu-Leu-Rink AmideMBHA树脂(0.125mmol) 和实施例14的喜树碱-20- (S) -
(0. 138mmol ， 1. leq.)以及 DIC(O. 55mmol，4. 4. eq.)和HOBt (0. 275mmol，2. 2eq.)的混合物振摇5天。用TFA、 H20和 TIS (9. 5mL/0. 85mL/0. 8mL)溶液处理2个小时，使肽从树脂上分离。滤除树脂，用二乙醚使 肽沉淀。离心悬浮液，得到球形粗产物肽。用制备型HPLC系统纯化粗产物，使用的色谱柱 为MicrosorbC^柱，从100% A和0% B至20% A和80% B，线性梯度洗脱80分钟。A为含 0. 1% TFA的水溶液，B为含0. 1% TFA的丙腈溶液。利用分析型HPLC检测各部分洗脱液。 收集含有目标产物的洗脱液，冻干。分析型HPLC得到的纯度为96. 1%。 ESI MS分析的分 子量为2172. 9 (与计算的分子量2173. 44相符)。
实施例29 喜树碱-20- (S) -0-甘氨酰_琥珀酰-A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Val- P Ala
■Aepa-(Doc)4-Gln-Trp-Ala-Val匿pAla-His-Leu-Leu-NH:
164-His_Leu_Leu_NH:
<formula>formula see original document page 165</formula>
■Aepa-(Do'c)4-DPhe-Gln-Trp-Ala-Val-pAla-His-Leu-Leu-NH基本按照实施例28的方法合成标题肽。分析型HPLC得到的纯度为99. 9% 。 ESIMS 分析的分子量为2321. 1 (与计算的分子量2320. 62相符)。
实施例30 喜树碱-20- (S) -0-甘氨酰_琥珀酰-A印a- (Doc) 2-Gln-Trp-Ala_Val- P Ala-His_
Leu_Leu_NH2<formula>formula see original document page 165</formula> 基本按照实施例28的方法合成标题肽。分析型HPLC得到的纯度为99. 9% 。 ESI MS分析的分子量为1882. 8 (与计算的分子量1883. 13相符)。
实施例31 喜树碱-20- (S) -0-甘氨酰_琥珀酰-A印a- (Doc) 2-DPhe-Gln-Trp-Ala_Val- P Ala
_His_Leu_Leu_NH2<formula>formula see original document page 165</formula> 基本按照实施例28的方法合成标题肽。分析型HPLC得到的纯度为99. 9% 。 ESI MS分析的分子量为2030. 7 (与计算的分子量2030. 30相符)。
实施例32 喜树碱-20- (S) -0-甘氨酰_琥珀酰-A印a- (Doc) 4-Gaba-Gln-Trp-Ala-Val- P Ala
-His-Leu-Nle-NH2<formula>formula see original document page 165</formula> 利用A印a- (Doc) 4-Gaba_Gln (Trt) -Trp (Boc) -Ala-Val- P Ala-His (Trt) -Leu-Nle -Rink Amide MBHA树脂，基本按照实施例28的方法合成标题肽。
实施例33pGlu-Hi s (Trt) _Trp (Boc) _Ser (tBu) _Tyr (tBu) -DLys [NE -A印a] -Leu-Arg (Pbf) _P
'Aepa-(DoG)2-Gln-T「p-Ala-Val-pAia-His-Leu-Leu-NH:
A印a-(Dot)2-DPhe-Gln-Trp-Ala-Vai-卩Ala-Hi卜Leu-Leu-NH.
■Aepa-(Doc)4-Gaba-Gln-Trp-Ala-Val-pAla-His-Leu-Nle-NH.ro-Gly-Rink Amide MBHA树月旨 基本按照实施例1的方法合成标题肽_树脂。Fmoc-Arg(Pbf)-OH， Fmoc_Ser(tBu)_0H， Fmoc_His(Trt)_0H， Fmoc_Pro_0H， Fmoc_Gly_0H， Fmoc_Leu_0H， Fmoc-DLys(Dde)_0H购 自Novabiochem， San Diego， CA。 pGlu-0H购 自Chem-Impex Internatoinal， Wood Dale, IL。以0. 25,1的规模合成。用含有20^哌啶的N-甲基妣 咯烷酮(MP)处理30分钟以去除Fmoc基团。得到pGlu-His (Trt)-Trp (Boc)-Ser (tBu) _T yr (tBu) -DLys (Dde) -Leu-Arg (Pbf) -Pro-Gly-Rink Amide MBHA树脂后，将保护的肽_树脂 移至振摇器上的反应瓶内用于人工合成。用含2X肼的DMF溶液处理半个小时去除DLys残 基上的Dde保护基。用DMF、 MeOH和DCM彻底清洗树脂，然后与预活化的Fmoc-A印a-0H的 酯溶液(如实施例4所述)在含有0. 5mL DIEA的DMF溶液中振摇2个小时。用DMF清洗 树脂，用含有20 %哌啶的DMF溶液处理树脂以去除A印a残基上的Fmoc保护基。用DMF和 DCM彻底清洗保护的肽-树脂。
实施例34 pGlu-Hi s (Trt) _Trp (Boc) _Ser (tBu) _Tyr (tBu) -DLys [NE _ (A印a- (Doc) 4_) ] _Leu_ Arg(Pbf)-Pro-Gly-Rink Amide MBHA树脂 利用实施例33的pGlu-His (Trt)-Trp (Boc)-Ser (tBu)-Tyr (tBu)-DLys [『-A印a ]-Leu-Arg(Pbf)-Pro-Gly-Rink Amide MBHA树脂，基本按照实施例2的方法合成标题保护 的肽树脂。 实施例35H_ (Doc) 4-A印a-Caeg-DCys (Trt) _3Pal_DTrp (Boc) _Lys (Boc) _DCys (Trt )-Thr(Bzl)-Tyr (tBu)-Rink Amide MBHA树脂 基本按照实施例5的方法合成标题保护的肽树脂。Fmoc-Thr (Bz 1) _0H、 Fmoc-DCys (Trt) _0H禾口 Fmoc_3Pal_0H源自Chem-Impex Internatoinal， WoodDale， IL。 Fmoc-DTrp (Boc) _0H、Fmoc_Lys (Boc) -OH禾口 Fmoc-Tyr (tBu) _0H源自AnaSpec， San Jose， CA。 Fmoc-Caeg (Bhoc) _0H源自P印S印tive Biosystems， Framingham， Mass。
实施例36 H_ (Doc)厂A印a-DPhe-Cys (Trt) _3ITyr_DTrp (Boc) _Lys (Boc) _Val_Cys (Trt) _Thr (tBu)-Rink Amide MBHA树月旨 基本按照实施例5的方法合成标题保护的肽树脂。Fmoc-3ITyr-0H和
Fmoc_DPhe_0H源自Chem_Impex Internatoinal, Wood Dale, IL。 实施例37 紫杉醇-2'-0-甘氨酰
向Boc-Gly-0H(53mg)和紫杉醇(215mg)的10mL 二氯甲烷溶液中，加入4_ 二甲氨 基吡啶(DMAP， 10mg)，然后加入EDC(58mg)。室温搅拌过夜后，用20mL二氯甲烷稀释反应液， 用10%柠檬酸水溶液、饱和的NaHC03和水洗涤混合物，然后用MgS04干燥，过滤。减压蒸除 滤液中的溶剂。用30XTFA二氯甲烷溶液室温处理粗产物45分钟。减压除去TFA和溶剂， 得到固体0.256g。 ESI MS分析的分子量为911.0(与计算的分子量911. l相符)。
实施例38 紫杉醇-2' -0- (N-甘氨酰-琥珀酰)
<formula>formula see original document page 167</formula> 将紫杉醇-2' -0-甘氨酰三氟乙酸盐(127mg， leq.)和琥珀酸酐(150mg， 12eq)在 5mL吡啶中的混合物室温搅拌过夜。减压蒸除溶剂。残余物用水研磨l个小时，过滤，收集 沉淀物。用水洗涤固体，干燥，得到固体94.8 mg。 ESIMS分析的分子量为1010. 9与计算的 1011. 06相符)。
实施例39 紫杉醇-2' -0- (N-缬氨酰_琥珀酰)
<formula>formula see original document page 167</formula> 利用Boc-Val-OH，基本按照实施例37和38的方法合成标题化合物。ESIMS分析 的分子量为1052. 5 (与计算的分子量1053. 27相符)。
实施例40
紫杉醇_2，-0-Gly-琥珀酰-A印a-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu
-Cys)-Thr-NH2 将5mL DCM中的H—A印a—Lys (Boc) —DTyr (tBu) —DTyr (tBu) —Cys (Trt) —Tyr (tBu)-DTrp (Boc) -Lys (Boc) -Abu-Cys (Trt) -Rink Amide MBHA树脂(实施例4) (0. 1,1)、紫杉 醇-2'-0-(N-甘氨酰-琥珀酰)(实施例39) (1. leq.)、DIC(136iiL，4. 4eq.)和H0AT(30mg， 1. leq.)的混合物振摇2天。相继用DMF、甲醇和DCM清洗树脂。空气中干燥后，用TFA、H20 和三异丙基硅烷(TIS)(9. 5 mL/0.85 mL/0. 8mL)的混合物处理树脂2个小时。滤除树脂， 滤液倒入IOO mL冷醚中。离心，收集沉淀。将粗产物溶于混合系统(100mL5X乙酸水溶
将、〉
液和30mL乙腈)中。向该溶液住滴加入碘甲醇直至黄色不再褪去。再搅拌反应液45分 钟。加入10%化25203水溶液以淬灭过量的碘。用制备型HPLC纯化溶液中的粗产物，所用 色谱柱为4x43cm的C18DYNAMAX-100A°(Varian， Walnut Creek， CA)。从80% A和20% B至 55% A和45% B，线性梯度洗脱50分钟，其中A为含O. 1% TFA的水溶液，B为含0. 1% TFA 的乙腈溶液。通过分析型HPLC检测各洗脱液。收集含有纯净产物的洗脱液，然后冻干。分 析型HPLC得到的纯度为98%。 ESI MS分析的分子量为2500. 9 (与计算的分子量2501.0 相符)。 实施例41 紫杉醇_2' -O-Val-琥珀酰-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2
DPhe~cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2 基本按照实施例40的方法合成标题肽。分析型HPLC得到的纯度为99% 。 ESI MS 分析的分子量为2066. 2 (与计算的分子量2067. 4相符)。
实施例42 紫杉醇_2，-0-Val-琥珀酰-A印a-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu
-Cys)-Thr-NH2
一一O
A^s^^pa-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-AbLi-Cys)-Thr-NH2
168CN 101791409 A 基本按照实施例40的方法合成标题肽。分析型HPLC得到的纯度为95% 。 ESI MS 分析的分子量为2544. 3 (与计算的分子量2543. 9相符)。
实施例43 N-Boc-阿霉素-14-0- (Fmoc-甘氨酸)酯
向DMF(5mL)中的阿霉素_HC1 (190mg)溶液加入(BOC)20(1. 2eq)，然后加入二乙 丙基乙基胺(2.5 eq.)。搅拌3个小时后，减压除去易挥发物质。用水处理残余物。过滤， 收集固体，用水洗涤固体，干燥。将所得产物溶于DMF(10mL)中。然后向该DMF溶液中加入 Fmoc-Gly-OH(l. 2eq. ) 、DMAP (0. 2eq.)和EDC (1. 2eq)，室温搅拌该混合液4个小时。蒸除溶 剂后，残余物在氯仿-甲醇和水之间进行分配。用MgS(^干燥有机层，然后过滤。减压蒸除 溶剂，残余物用硅胶色谱进行纯化，流动相为氯仿-甲醇(9 : 1)。收集含目标产物的各洗
脱液，然后减压蒸除溶剂。
实施例44 N-BOC-阿霉素-14-0- [ (N_琥珀酰)甘氨酸]酉旨
向Boc-阿霉素-14-0-(Fmoc-甘氨酸)酉旨(lOOmg)的DMF(5mL)溶液中加入lmL 哌啶。室温搅拌2个小时后，用氯仿(20mL)进行稀释。用盐水洗涤混合物，MgS(^干燥，过 滤。减压蒸除溶剂至体积为约5mL。向该混合物中加入琥珀酸酐(4eq.)、DMAP(2eq.)和三 乙胺(4eq.)，然后室温下搅拌该溶液过夜。减压蒸除易挥发物质。用5%柠檬酸水溶液研
磨该残余物，然后过滤收集沉淀物，然后用水洗涤沉淀物，最后干燥。
实施例45 pGlu-His-Trp-Ser-Tyr-DLys [ ff _ (阿霉素-14-0-甘氨酰_琥珀酰-A印a- (Doc) 4-)]-Leu-Arg-Pro-Gly-NH2 基本按照实施例28的方法，用pGlu-His (Trt) -Trp (Boc) -Ser (tBu) -Tyr (tBu) -D Lys [ !Sp _ (A印a- (Doc) 4-) ] -Leu-Arg (Pbf) -Pro-Gly-Rink Amide MBHA树脂(实施例34)和
169Boc-阿霉素-14-0-[ (N-琥珀酰)甘氨酸]酯(实施例44)合成标题化合物。
实施例46 pGlu-His-Trp-Ser-Tyr-DLys [ :N飞_ (阿霉素-14-0-Gly-琥珀酰_ (Doc) 4-Gaba_)-
Leu_Arg_Pro_Gly_NH2 基本按照实施例45的方法合成标题化合物。Fmoc-Gaba-OH源自Novabiochem, San
Diego， CA。 实施例47 阿霉素-14-0-甘氨酰_琥珀酰_ (Doc) 4-A印a-Caeg-cycl0 (DCys-3Pal-DTrp-Lys-
DCys)-Thr (Bzl)-Tyr_NH2 基本按照实施例19的方法，用H-(Doc)4-A印a-Caeg-DCys(Trt)-3Pal-Trp(Boc)-Lys (Boc) -DCys (Trt) -Thr (Bzl) -Tyr (tBu) -Rink Amide MBHA树脂(实施例35)和BOC-阿 霉素-14-0-[ (N-琥珀酰)甘氨酸]酯(实施例44)合成标题化合物。
实施例48 紫杉醇-2'-0-甘氨酰_琥珀酰-(Doc)4-A印a-DPhe-cyclo[Cys-3ITyr-DTrp-Lys
-Val-Cys]-Thr-NH2 基本按照实施例40的方法，用H- (Doc) 4-A印a-DPhe-Cys (Trt) -3ITyr-DTrp ( Boc)-Lys(Boc)-Val-Cys(Trt)-Thr(tBu)-Rink Amide MBHA树脂(实施例36)和紫杉 醇-2' -O-(N-甘氨酰-琥珀酰)(实施例38)合成标题化合物。
实施例49 紫杉醇-2 ， -0-甘氨酰_琥珀酰-A印a- (Doc) 2-Gln-Trp-Ala_Val- P Ala-His-Phe-
Nle-NH2
.(Doc)4-Aepa-Caeg-cyclo(DCys-3Pat-DTrp-Lys-DCys)-Thr(Bzl)-Tyr-NH2
i-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr-NH.'Aepa-(Doc)2匿Gln-Trp-Ala-Va卜pAla-His-Phe-Nle-NH: 基本按照实施例28的方法，用H-A印a-(Doc)2-Gln(Trt)-Trp(Boc)-Ala-Val-PA la-His (Trt) -Phe-Nle-Rink Amide MBHA树脂和紫杉醇_2' -0- (N-甘氨酰-琥珀酰)(实 施例38)合成标题化合物。
实施例50 pGlu-Hi s-Trp-Ser-Tyr-DLys [ N~￡ _ (紫杉醇_2 ， _0_甘氨酰_琥珀酰-A印a- (Doc
)4-)]-Leu-Arg-Pro-Gly-NH2基本按照实施例45的方法，用pGlu-His (Trt) -Trp (Boc) -Ser (tBu) -Tyr (tBu) -D Lys[NE-(A印a-(Doc)4-)]-Leu-Arg(Pbf)-Pro-Gly-Rink Amide MBHA树月旨(实施例34)和 2' -O-(N-琥珀酰-甘氨酰)_紫杉醇(实施例38)合成标题化合物。
实施例51 pGlu-Hi s-Trp-Ser-Tyr-DLy s [ N飞_ (喜树碱-20- (S) _0_甘氨酰_琥珀酰_ (Doc) 4
_Aepa_)]_Leu_Arg_Pro_Gly_NH2 基本按照实施例50的方法，用喜树碱-20- (S) -
(实施 例14)合成标题化合物。 实施例52
基本按照实施例19的方法合成标题化合物。收率=11 % ，分析型HPLC所得纯度 为99. 9%。 ESI MS分析的分子量为1891. 8(与计算的分子量1891. 1相符)。
实施例53
2
Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH:
171
喜树碱-Gly-戊二酰-Lys-DTyr-DTyr-环(Cys-Tyr-DTrp-Lys-Abu-Cys) -Thr-NH
Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2 基本按照实施例19的方法合成标题化合物。收率=23% ，分析型HPLC所得纯度 为99%。 ESI MS分析的分子量为1841.9(与计算的分子量1841. l相符)。
实施例54 喜树碱-Gly-琥珀酰_ (Doc) 6-DPhe_c (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2
(Doc)6-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2 基本按照实施例19的方法合成标题化合物。收率=18% ，分析型HPLC所得纯度 为98%。 ESI MS分析的分子量为2390. 0(与计算的分子量2390. 7相符)。
实施例55 喜树碱-Gly-戊二酰-Lys-Lys-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-C
ys) -Thr-NH2
,Lys-Lys-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abi>Cys)-Thr-NH2 基本按照实施例19的方法合成标题化合物。收率=12% ，分析型HPLC所得纯度 为100%。 ESI MS分析的分子量为2097.0(与计算的分子量2097.4相符)。
实施例56 喜树碱-Gly-琥珀酰_ (Doc) 4-DPhe-c (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2
(Doc)4-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2 基本按照实施例1 9的方法合成标题化合物。收率=31 % ，分析型HPLC所得纯度 为100%。 ESI MS分析的分子量为2100.9(与计算的分子量2100.3相符)。
实施例57 喜树碱-Gly-琥珀酰-A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2
Aepa-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2 基本按照实施例19的方法合成标题化合物。收率=21 % ，分析型HPLC所得纯度为97%。 ESI MS分析的分子量为1688.0(与计算的分子量1688.9相符)。
实施例58 喜树碱-Abu-琥珀酰_ (Doc) 4-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cy
s) -Thr-NH2
(Doc)4-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH: 基本按照实施例19的方法合成标题化合物。收率=23% ，分析型HPLC所得纯度 为95%。 ESI MS分析的分子量为2435.2(与计算的分子量2435.8相符)。
实施例59 喜树碱_戊二酰_ (Doc) 2-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _T
hr-NH2
(Doc)2-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2 基本按照实施例19的方法合成标题化合物。收率=11 % ，分析型HPLC所得纯度 为95%。 ESI MS分析的分子量为2074.0(与计算的分子量2074.4相符)。
实施例60 喜树碱_戊二酰-Doc-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_
NH2
Doc-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr掘: 基本按照实施例19的方法合成标题化合物。收率=16% ，分析型HPLC所得纯度 为95%。 ESI MS分析的分子量为1929.5(与计算的分子量1929.2相符)。
实施例61 喜树碱-20-甘氨酰_琥珀酰-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2
DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH: 基本按照实施例19的方法合成标题化合物。收率=15. 6% ，分析型HPLC所得纯 度为94%。 ESI MS分析的分子量为1520. 1 (与计算的分子量1519.71相符)。
实施例62 {5_(R)_乙基-9， 10-二氟_1，4，5， 13-四氢_3H， 15H_氧杂卓并[3'，4' :6，7]中 氮茚并[1 ， 2-b]喹啉-3， 15- 二酮-5-0-甘氨酰_琥珀酰} _ (Doc) 4-A印a-DPhe-cydo (Cys-
173Tyr_DTrp_Lys_Abu_Cys)-Thr-NH:
<formula>formula see original document page 174</formula>
(Doc),Aepa-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH: 基本按照实施例19的方法合成标题化合物。收率=25% ，分析型HPLC所得纯度 为97%。 ESI MS分析的分子量为2320.0(与计算的分子量23 19. 6相符)。
实施例63 {5_(R)_乙基-9， 10-二氟_1，4，5， 13-四氢_3H， 15H_氧杂卓并[3'，4' :6，7]中 氮茚并[1， 2-b]喹啉-3， 15- 二酮-5-0-甘氨酰_戊二酰} -A印a-Lys-DTyr-DTyr-cyclo (Cy s_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
<formula>formula see original document page 174</formula> 基本按照实施例19的方法合成标题化合物。收率=24% ，分析型HPLC所得纯度 为95%。 ESI MS分析的分子量为2059. 4(与计算的分子量2060. 3相符)。
实施例64 (5-(R)_乙基-9，10-二氟_1，4，5，13-四氢_3H， 15H_氧杂卓并[3'，4' :6，7]中 氮茚并[1 ， 2-b]喹啉-3， 15- 二酮-5-0-甘氨酰-琥珀酰} _ (Doc) 4-A印a-Lys-DTyr-DTyr-c (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
<formula>formula see original document page 174</formula> 基本按照实施例19的方法合成标题化合物。收率=48% ，分析型HPLC所得纯度 为99. 9% 。 ESI MS分析的分子量为2626. 0 (与计算的分子量2626. 9相符)。
实施例65 喜树碱-20-戊二酰_ (Doc) 4-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys
)-Thr-NH2<formula>formula see original document page 174</formula> 基本按照实施例19的方法合成标题化合物。收率=10% ，分析型HPLC所得纯度 为98. 9%。 ESI MS分析的分子量为2365. 0(与计算的分子量2365. 0相符)。
实施例66 H-DPhe-Cys(Trt)-Tyr(tBu)-DTrp(Boc)-Lys(Aloe)-Abu-Cys(Trt)-Thr(tBu)-Ri nk-Amide-MBHA-树脂
Aepa-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH:
(Doc)4-Aepa-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH:
.(Doc)4-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys>-Thr-NH:
基于芴甲氧羰基(Fmoc)化学保护方法，用应用生物系统(Foster City， CA)433A型肽合成仪自动合成标题肽。使用0. 72 mmol/g取代的Rink AmideMBHA树脂 (Novabiochem， San Diego， CA)。采用的Fmoc氨基酸(AnaSpec， Sanjose， CA)具有如下侧 链保护Fmoc-Thr (tBu) _0H， Fmoc-Cys (Trt) _0H， Fmoc-Lys (Aloe) _0H， Fmoc-DTrp (Boc) _0H， Fmoc-Tyr(0tBu)-0H， Fmoc-DPhe-OH和Fmoc-Abu-0H。以0. 25 mmol规模进行合成。用含 20%哌啶的^甲基吡咯烷酮(NMP)溶液处理30分钟去除Fmoc基团。在各偶联步骤中，首 先将Fmoc氨基酸(4eq，l翻l)在含有0. 45M 2_ (1_H_苯并三唑_1_基)_1， 1， 2， 3_四甲基 脲鎗六氟磷酸酯/1-羟基-苯并三唑(HBTU/H0BT)的DMF溶液中预活化。将得到的活化氨 基酸酯、lmL二异丙基乙基胺(DIEA)和lmLNMP加到树脂中。设定ABI433A肽合成仪的程序 进行下列反应循环(1)用NMP清洗，(2)用含20%哌啶的NMP溶液处理30分钟，去除Fmoc 保护基，(3)用NMP清洗，(4)与预先活化的Fmoc氨基酸偶联l个小时。对于Cys(Trt)2、 Tyr(tBu"和DTrp(Boc"，采用的是单偶联法。其它氨基酸采用双偶联法。根据序列将残基 逐个偶联到树脂上。肽链偶联完毕后，去除Fmoc，用DMF和二氯甲烷(DCM)彻底清洗树脂。
实施例67 Fmoc-A印a-DPhe-Cys (Trt) _Tyr (tBu) _DTrp (Boc) _Lys (Aloe) _Abu_Cys (Trt) _Thr (tBu) -Rink-Amide-MBHA-树脂 从实施例66的肽开始合成标题肽。将Fmoc-A印a-OH(NeosystemLaboratoire， Gennevilliers， France. 1. 5eq，0. 75mmol)用含有0_(7_氮杂苯并三唑_1_基)_1， 1，3， 3-四甲基脲鎗六氟磷酸酯(HATU，1.4eq，0. 7mmo1)和1_羟基_7_氮杂苯并三唑(H0AT， 1.4eq. ，0. 7mmo1)的2mL DMF溶液预活化5分钟。将上述树脂移至小反应瓶中，并与活化的 Fmoc-A印a-0H的酯以及lmL DIEA —同在振摇器上振摇2个小时。用DMF和DCM彻底清洗 树脂。 实施例68 H-Doc-Doc-Doc-Doc-A印a-DPhe-Cys (Trt) -Tyr (tBu) -DTrp (Boc) -Lys (Aloe) -Abu -Cys (Trt) -Thr (tBu) -Rink-Amide-MBHA-树脂 从实施例68的肽开始合成标题肽。用DMF清洗树脂后，用含25%哌啶的DMF溶 液处理丰对月旨，除去Fmoc。 i亥丰对月旨与Fmoc_Doc_OH(Chem_ImpexInternatoinal， Wood Dale, IL. ， 1. 5eq， 0. 75mmol) 、 N， N_ 二异丙基碳二酰亚胺(DIC， 1. 5eq， 0. 75mmol)和H0BT (1. 5eq， 0. 75mmol)的DMF溶液混合2个小时。如偶联第一个Fmoc-Doc-OH的相同方法，将第2至第 4个Fmoc-Doc-OH偶联到树脂上。重复该方法直至肽链完成偶联。
用含25%哌啶的DMF溶液除去Fmoc。用DMF和DCM清洗树脂。
实施例69 H_Doc_Doc_Doc_Doc_Aepa_DPhe_cyclo(Cys-Tyr-DTrp-Lys(Aloe)_Abu_Cys)-Thr _NH2 用19mL TFA (三氟乙酸，Halocarbon Products Corp. River Edge, NJ) 、 1. 6mL TIS(三异丙基硅烷，Aldrich)和1. 7mL水将肽从树脂上切断，进行2个小时。滤除树脂， 将肽倾入醚中得到沉淀。将沉淀物溶于150 mL的5X醋酸和30mL的乙腈中。逐滴加入碘 (20mg/ml，在Me0H中)直至红色不再褪去。将烧瓶置于热水浴中，搅拌2个小时。用10% Na2SS03淬灭该反应。用PhenomenexC18色谱柱纯化所得肽，用5-60% CH3CN进行梯度洗脱，其中，Buffer A是含0. 1 % TFA的水溶液，Buffer B是含0. 1 % TFA的CH3CN溶液，洗脱60 分钟以上。将含有产物的洗脱部分冻干，得到186mg(收率40X)的白色粉末。MS(电喷 雾):1722. 2。
实施例70 H-Doc-Doc-Doc-A印a-DPhe-Cys (Trt) -Tyr (tBu) -DTrp (Boc) -Lys (Aloe) -Abu-Cys (Trt) -Thr (tBu) -Rink-Amide-MBHA-树脂 从实施例67的肽开始合成标题肽。用DMF清洗树脂后，用含25%哌啶的DMF溶 液处理丰对月旨，除去Fmoc。 i亥丰对月旨与Fmoc_Doc_OH(Chem_ImpexInternatoinal， Wood Dale, IL， 1. 5eq，0. 75mmol) 、 N， N_ 二异丙基碳二酰亚胺(DIC， 1. 5eq，0. 75mmol)和HOBT(l. 5eq， 0. 75mmol)的DMF溶液混合2个小时。如偶联第一个Fmoc-Doc-OH的相同方法，将第2至第 3个Fmoc-Doc-0H偶联到树脂上。重复该方法直至肽链完成偶联。用含25X哌啶的DMF溶 液除去最后的Fmoc。用DMF和DCM清洗树脂。
实施例71 H-Doc-Doc-Doc-A印a-DPhe-cycl0 (Cys_Tyr_DTrp_Lys (Aloe) _Abu_Cys) _Thr_NH2 用19mL TFA(三氟乙酸，Halocarbon Products Corp. River Edge，NJ) 、1. 6mLTIS(三异丙基 硅烷，Aldrich)和1. 7mL的水将肽从树脂上切断，进行2个小时。滤除树脂，将肽倾入醚中 得到沉淀。将沉淀物溶于150 mL的5X醋酸和30mL的乙腈中。逐滴加入碘(20mg/ml，在 Me0H中)直至红色不再褪去。将烧瓶置于热水浴中，搅拌2个小时。用10% Na2SS03淬灭 该反应。用PhenomenexC^色谱柱纯化所得肽，用5-60% CH3CN进行梯度洗脱，其中，Buffer A是含0. 1 % TFA的水溶液，Buf f er B是含0. 1 % TFA的CH3CN溶液，洗脱60分钟以上。将 含有产物的洗脱部分冻干，得到180mg(收率42X)的白色粉末。MS(电喷雾)1722.2。
实施例72
紫杉醇-2'-戊二酸
向紫杉醇(HandeTech USA， Inc， Houston, Texas, lg. ， 1. 17mmol)的吡啶(10mL)溶
液加入戊二酸酐(Aldrich， 1. 6 g， 14. lmmol， 12eq.)。室温下搅拌该溶液4个小时，然后减
压蒸馏。加入20ml的水。过滤，得到粘性固体。用丙酮/水重结晶，得到0.842 g的白色
固体，O. 869mmole，收率74%。 MS(电喷雾):969.0。 实施例73 紫杉醇-2' -Doc-Suc-OH或
N_Suc-OH
H 在紫杉醇(lg. ， 1. 17mmol)和Boc-Doc-0H(0. 31g. ， 1. 17mmol)的DCM(25mL)溶液 中，加入DIC(O. 241mL， 1. 54mmol)，然后加入DMAP(50mg. 0. 4mmo1)。所得溶液在室温下搅 拌4个小时。用3X10X柠檬酸、3X饱和的NaHC03、lx饱和的NaCl洗涤所得溶液，用MgS04 干燥。过滤，蒸馏。将所得残余物溶于EtOAc中，然后用正己烷进行沉淀。过滤，得到沉 淀的产物，减压干燥，得到固体(1. 19g，1.08mmo1)。收率为92%。 MS(电喷雾)m/e = 1099. 7 (+1) ， HPLC所分析的纯度为95%。将得到的Boc-Doc-紫杉醇(1. 19g， 1. 08,1)溶 于20mL的甲酸中，搅拌30分钟，然后蒸馏。将产物溶于15mL的吡啶中。向该溶液加入琥 珀酸酐(1. 29g， 13mmol)。室温下搅拌混合物过夜，减压蒸除吡啶。加水研磨使残余物成粉 末，收集到0. 99g(0. 91mmole，收率:84% ) 。 MS(电喷雾)1099. 4 (+1) ， 1121. 6(Na+l) 。 HPLC 分析的纯度为75%。
实施例74 紫杉醇_2，-戊二酰_(00(3)4^印&-0 116-07(;10(078-171-011"-1^8^1311^^8)-111
r-NH2
(Doc)4-Aepa-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2 向实施例69的肽(125mg，0. 067mmol)的DMF(10mL)溶液中，加入紫杉 醇-2， -Glut-OH(实施例72，65mg，0. 067mmol) 、 H0BT(20mg，0. 147mmool、 BOP(苯并三唑-l-基-氧-三(二甲基氨基)-磷鎗六氟代磷酸盐，Benzotriazole-l-yl-oxy-tris-(dimethyl咖ino)-phosphonium hexaf luorophosphate ;29mg， 0. 067mmol) 禾口 DIEA(8eq.， 93i！ L)。搅拌所得溶液过夜，然后减压蒸除溶剂。将残余物溶于最小量的MeOH中，然后加醚 产生沉淀，得到固体(108 mg，O. 04mmol)。收率为60%。 MS(电喷雾)1409. 5 (+2)。为了除 去Lys上的Aloc，将肽溶于DCM/THF (无水，15mL/5mL)中，然后，(TC下，加入冰醋酸(15 y L， 5eq. )、 Pd(PPh3)4(四(三苯基膦)钯，Tetrakis (triphenylphosphine)palladi咖(O); 12mg，0.3 eq.)和Bu3SnH(氢化三丁基锡，Tributyltin hydride ;2 X 31 ii L， 3eq)。搅拌1 个小时，用含O. 5M HC1的醚(0. 7mL， lOeq.)淬灭该溶液的反应。加醚使肽沉淀。用PLRP-S 柱(Polymer Labs， 100A， 8 y )纯化粗产物，5-90 %梯度洗脱1个小时，其中溶剂A是含 5% MeOH的水溶液，溶剂B是CH3CN。合并纯净组分，冻干，得到42mg的肽。MS (电喷雾) 2731. 4(与计算的分子量2732. 1相符)。HPLC分析的纯度为99. 9%。
实施例75 紫杉醇-2， -0。(3-511(;-(00(;)3^印&-0 116-07(;10(〇78-171-011卬-1^8^1311-〇78)-111 r-NH9 向实施例71的肽(200mg，0. 12mmol)的DMF(10ml)溶液中加入紫杉 醇-2， -Doc-Suc-OH(实施例73， 140mg，0. 128mmol) 、 H0BT(39mg，0. 281mmol) 、 B0P(74mg， 0. 166mmol)和DIEA(8eq. ，177iiL)。搅拌该溶液过夜。减压蒸馏。得到固体(355mg， 0. 126,1)。 为了除去Lys上的Aloc，将产物溶于DCM/THF(无水，15mL/5mL)中，然后，(TC下， 加入冰醋酸(19ii L，5eq. ) 、Pd(PPh3)4(12mg，0. 3eq.)和Bu3SnH(2 X 54 ii L， 3eq)。搅拌1个 小时，然后用含O. 5M HC1的醚(0. 7mL， lOeq.)淬灭该溶液的反应。加醚使产物沉淀。用 PLRP-S柱(Polymer Labs， IOOA， 8 y )纯化粗产物，5_90%梯度洗脱1个小时，其中溶剂A是 含5% MeOH的水溶液，溶剂B是CH3CN。合并纯净组分，冻干。MS(电喷雾)2717. 3 (与计 算的分子量2718. 1相符)。HPLC分析的纯度为99. 9% 。
实施例76 紫杉醇-5&1-511(3-(00(;)4^印&-0 116-07(;10(〇78-171-011卬-1^8^1311-〇78)-1111-" H9
力一Suc-(Doc〉3-Aepa-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys〉-Thr-NH.'Y(Doc)4-Aepa-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-丁i'!r-Nih- 用2'-0-(N-琥珀酰-N-甲基-甘氨酰)_紫杉醇(实施例38)和H-Doc-Doc-Doc -Doc-A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys (Aloe) -Abu-Cys) _Thr_NH2 (实施例69)，基本按 照实施例28的方法合成标题化合物。收率为18. 8%，HPLC分析的纯度为95%。分子量为 2789.2。 实施例77 紫杉醇-Sue- (Doc) 4-Gaba-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2
<formula>formula see original document page 179</formula> 基本按照实施例28的方法，用紫杉醇_2'-琥珀酰(如实施例72中制备的)，琥 珀酸酐代替戊二酸酐以及基本按照实施例1方法制备的肽H-Doc-Doc-Doc-Doc-Gaba-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2合成标题化合物，然后如实施例2所述的方法偶联4 个Doc残基。收率为12. 1X，HPLC分析的纯度为97X。测定的分子量为2537. 8。
实施例78 紫杉醇-Sar-Suc- (Doc) 4-A印a-Gaba-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH2
(Doc)4-Aepa-Gaba-Gln-Trp-Ala-Val-pAla-His-Leu-Nle-NH2 基本按照实施例28的方法，用紫杉醇_2'-0- (N_琥珀酰_N_甲基-甘氨酰)(基本 上如实施例38的制备)，用Boc-Sar-0H代替Boc-Gly-0H以及如实施例1的方法合成的肽H -(Doc) 4-A印a-Gaba-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle_NH2合成标题化合物。然后，如 实施例4所述偶联一个A印a残基，再如实施例5所述偶联4个Doc残基。收率为13.4%， HPLC分析的纯度为98%。测定的分子量为2778. 1。
实施例79 喜树碱-Gly-Suc- (Doc) 4-A印a-Gaba-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH2
画(Doc)4-A印a-Gaba-Gln-Trp-Ala-Val-卩Ala-His-Leu-Nle-NH: 基本上按照实施例28的方法，用喜树碱-20-(S)-
d 施例14)和H-(Doc)f Aeoa-Gaba-Gln-Tro-Ala-Val- |3 Ala-His-Leu-Nle-NH。(实施例78) 合成标题化合物。收率为14. 4%， HPLC分析的纯度为99. 4%。测定的分子量为2258。
Table (表)A_I中的其他化合物可根据上述方法进行合成。 -A印a- (Doc) 4-Gaba-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle-NH: - (Doc) 4-A印a-Gaba-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH: -A印a- (Doc) 2-Gln-Trp-Ala_Val- P Ala—His-Leu-Leu_NH2 -A印a- (Doc) 2-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle_NH2 -A印a- (Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -A印a- (Doc) 2-Gln-Trp-Ala_Val- P Ala-His-Phe-Nle_NH2 -A印a- (Doc) 2-Gln-Trp-Ala_Ala- P Ala-His-Phe-Nle_NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2

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- (Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH2 - (Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2 -A印a-Doc-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 -A印a-Doc-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 4印&-00。-0 116-6111-11"^1&,&1-617-附8-1^11-1^11^112 -A印a-Doc-DPhe-Gln-Trp-Ala-Val- P Ala_His-Leu_Nle_NH2 -A印a-Doc-DPhe-Gln-Trp-Ala-Val- P Ala_His-Leu_Leu_NH2 -Doc-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -Doc-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Doc-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -Doc-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Doc-DPhe-Gln-Trp-Ala-Val-P Ala_His-Leu_Leu_NH2 - (Doc) 2-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 - (Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 - (Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Lau-NH2 - (Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 - (Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Lau-Leu_NH2 -A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 - (Doc) 4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2 - (Doc) 4-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2 -A印a-(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Lau_NH2 - (Doc) 4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2 - (Doc) 4-A印a-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu-NH: -A印a-(Doc)4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu-NH: - (Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala_H is-Leu-Leu_NH2 _ (Doc) 4_A，_Gaba_Gln_Trp_Ala_Val_ P Ala_His_Leu_Leu_NH2 -A印a- (Doc) 4_Gaba_Gln_Trp_Ala_Val_ P Ala_His_Leu_Leu_NH2 -(Doc)4-Gaba-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle-NH2 - (Doc) 4—A印a-Gaba-Gln-Trp-Ala-Va1— P Ala-His-Leu-Nle_NH2 -A印a- (Doc) 4-Gaba-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle_NH2 - (Doc) 2-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 - (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 - (Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 - (Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 - (Doc) 2-Gln-Trp-Ala-Val-P Ala—His-Leu-Leu_NH2 -A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -(00(3)4^印&-0 116-6111-11卬^1&,&1-617-附8-1^11-1^11^112 - (Doc) 4-A印a-DPhe-G ln-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2
- (Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Lau-Leu-NH: -A印a- (Doc) 4-DPhe-Gln_Trp-Ala-Ala- P Ala-His-Phe-Nle-NH: -A印a- (Doc) 4-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH: -A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Lau_NH2 -A印a- (Doc) 4-DPhe-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle-NH: -A印a- (Doc) 4-DPhe-Gln-Trp-Ala_Val- P Ala-His-Leu-Leu-NH: - (Doc) 4-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 - (Doc) 4-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -(Doc)4-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 - (Doc) 4-DPhe-Gln-Trp-Ala-Val-P Ala—H is-Leu-Nle_NH2 - (Doc) 4-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 - (Doc) 4-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH: - (Doc) 4-A印a-DAla-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH: - (Doc) 4-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 - (Doc) 4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle_NH2 - (Doc) 4—A印a-Gln-Trp-Ala-Va1— P Ala—His-Leu-Leu_NH2 -A印a- (Doc) 4-Gln-Trp-Ala_Ala- P Ala-His-Phe-Nle_NH2 -A印a- (Doc) 4-Gln-Trp-Ala_Val- P Ala-His-Phe-Nle-NH2 4印&-(00(3)4-6111-11卬41&,&1-617-附8-1^11-1^11^112 -A印a- (Doc) 4-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle-NH2 -A印a- (Doc) 4-Gln-Trp-Ala_Val- P Ala-His-Leu-Leu_NH2 - (Doc) 4-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 - (Doc) 4-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 - (Doc) 4-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 - (Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 - (Doc) 4-Gln-Trp-Ala-Val-P Ala—His-Leu-Leu_NH2 - (Doc) 4-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 - (Doc) 4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle_NH2 4印&-0 116-6111-11"^1&,&1-617-附8-1^11-1^11^112 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala_Ala- P Ala-His-Phe-Nle-NH: -A印a- (Doc) 2-DAla-Gln-Trp-Ala_Val- P Ala-His-Phe-Nle-NH: -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle-NH: -A印a- (Doc) 2-DPhe-Gln-Trp-Ala_Val- P Ala-His-Leu-Leu-NH: - (Doc) 2-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 - (Doc) 2-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -(Doc)2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2
- (Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 - (Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 -A印a-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle_NH2 -Aepa- (Doc) 4-Gln-Trp-Ala_Val- P Ala-His-Ala-Nle_NH2 -A印a- (Doc) 4-Gln-Trp-Ala_Val- P Ala-His-Ala-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle_NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala_Val- P Ala-His-Ala-Nle_NH2 -(Doc)2-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -A印a-(Doc)2-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc)2-A印a-DPhe-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc)2-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 - (Doc) 4-DPhe-G ln-Trp-Ala-Val-PAla-His-Ala-Nle-NH2 -(Doc)4-A印a-DPhe-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle_NH2 -A印a- (Doc) 4-DPhe-Gln-Trp-Ala_Val- P Ala-His-Ala-Nle-NH2 -(Doc)4-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc)4-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a- (Doc) 2-Gln-Trp-Ala_Val- P Ala-His-Ala-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 - (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala_Val- P Ala-His-Ala-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 _ (Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Ala-Nle-NH2 -A印a- (Doc) 4-Gln-Trp-Ala_Val- P Ala-His-Ala-Nle-NH2 - (Doc) 4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH2 - (Doc) 4-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -A印a- (Doc) 4-DPhe-Gln-Trp-Ala_Val- P Ala-His-Ala-Nle_NH2 - (Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle_NH2 -(Doc)4-DPhe-Gln-Trp-Ala-Val-P Ala-His-Ala-Nle-NH2 - (Doc) 2-A印a-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH2 - (Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH2 -A印a- (Doc) 3_Gln_Trp_Ala_Val_ P Ala_His_Leu_Leu_NH2 -A印a- (Doc) 3-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle_NH2 -A印a- (Doc) 3_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2 -A印a- (Doc) 3-Gln-Trp-Ala_Val- P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 3-Gln-Trp-Ala_Ala- P Ala-His-Phe-Nle_NH2 -A印a-Doc-Gln-Trp-Ala-Val- P Ala-His_Leu_Leu_NH2 -A印a-Doc-Gln-Trp-Ala-Val- P Ala_His-Leu_Nle_NH2































-Aepa_Doc_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2 -A印a-Doc-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-Doc-Gln-Trp-Ala-Ala- P Ala_His-Phe-Nle_NH2
(Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc
-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -A印a-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2
-A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -Doc-Gln-Trp-Ala-Val-Ala-His-Leu-Leu-NH2 -Doc-A印a-Gln-Trp-Ala-Ala- P Ala_His-Phe-Nle_NH2 -Doc-A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -Doc_Aepa_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2 -Doc-A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -Doc-A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -Doc-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Doc-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc) 4_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -(Doc) 4_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2<formula>formula see original document page 186</formula>,a-(Doc)3-[|
pGlu-His-Trp-Ser-Tyr — H "^"V" Leu-Arg-Pro-Gly-N H2
H O
_Aepa-(Doc)4 _N-H
pGlu-His-Trp-Ser-Tyr—N^Y~Leu-Arg-Pro-Gly-NH2
H O
-Aepa—N"iH 、
pGlu-His-Trp-Ser-Tyr-N"^Y" Leu-Arg-Pro-Gly-NH2H O
-(Doc)2-Aepa—y~|
pGlu-His-Trp-Ser-Tyr-。^-Leu-Arg-Pro-Gly-NH-(Doc)3-Aepa—fsj-
2
H
H 6
pGlu-His-Trp-Ser-Tyr-y^^pLeu-Arg-Pro-Gly-NH2
-A印a-Doc —N~|H 、
pGlu-His-Trp-Ser-Tyr-N""^^-Leu-Arg-Pro-Gly-NH2
H O
-(Doc)4-Aepa —N~jH 、
pGlu-His-Trp-Ser-Tyr—N^Y~Leu—Arg—Pro—G|y-NH2
H O
-Aepa-(Doc)2
H
pGlu-His-Trp-Ser-Tyr-J^^—Leu-Arg-Pro-Gly-NH
O
'2
-A^a-(Doc)3 —NnpGlu-His-Trp-Ser-Tyr—^j^_Leu_Arg_pro_Gly-NH2<formula>formula see original document page 188</formula><formula>formula see original document page 189</formula><formula>formula see original document page 190</formula> - (Doc) 2-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 - (Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 - (Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 - (Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 - (Doc) 2-Gln-Trp-Ala-Val-e Ala-His-Leu-Leu_NH2 -A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2 -A印a-Gln-Trp-Ala-Val- P Ala_His_Leu_Leu_NH2 -A印a- (Doc) 2-Gln-Trp-Ala_Ala- P Ala-His-Phe-Nle_NH2 -A印a- (Doc) 2-Gln-Trp-Ala_Val- P Ala-His-Phe-Nle_NH2 -A印a- (Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -A印a- (Doc) 2-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle_NH2 -A印a-(Doc) 2-Gln-Trp-Ala-Val-e Ala-His-Leu-Leu_NH2 - (Doc) 4-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 - (Doc) 4-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 - (Doc) 4-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 - (Doc) 4-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 - (Doc) 4-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 - (Doc) 4-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH: - (Doc) 4-A印a-DAla-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH: - (Doc) 4-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 - (Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH: - (Doc) 4-A印a-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu-NH: -A印a- (Doc) 4-DPhe-Gln_Trp-Ala-Ala- P Ala-His-Phe-Nle-NH: -A印a- (Doc) 4-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH: -A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -A印a- (Doc) 4-DPhe-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle-NH: -A印a- (Doc) 4-DPhe-Gln-Trp-Ala_Val- P Ala-His-Leu-Leu-NH: - (Doc) 4-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 - (Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 - (Doc) 4-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -(Doc)4-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle-NH2
190
-(Doc)4-Gln-Trp-Ala-Val-Ala-His-Leu-Leu-NH2-(Doc)4-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2-(Doc)4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH2-(Doc)4_Aepa_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2-(Doc)4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH2-(Doc)4-A印a-Gln-Trp-Ala-Val- P Ala_His_Leu_Leu_NH2-A印a-(Doc)4-Gln-Trp-Ala-Ala-PAla-His-Phe-Nle-NH2-A印a-(Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2-A印a-(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-A印a-(Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-A印a-(Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-(Doc)2-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2-(Doc)2-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2-(Doc)2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-(Doc)2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-(Doc)2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-A印a-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2-A印a-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-A印a-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-A印a-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-A印a-(Doc) 2-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle--NH2-A印a-(Doc) 2-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle--NH2-A印a-(Doc)2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2
-A印a-(Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle--NH2-A印a-(Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu--NH2-(Doc)2-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle--NH2-(Doc)2-A印a-DAla-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle--NH2-(Doc)2-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2
-(Doc)2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle--NH2-(Doc)2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu--NH2-(Doc)2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle--NH2-(Doc)2-A印a-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH2-(Doc)4-DPhe-Gln-Trp-Ala-Val-P Ala-His-Ala-Nle-NH2-(Doc)4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle--NH2-A印a-(Doc) 4-DPhe-Gln-Trp-Ala-Val-P Ala-His-Ala-Nle--NH2-(Doc)4-Gln-Trp-Ala-Val-P Ala-His-Ala-Nle-NH2-(Doc)4-A印a-Gln-Trp-Ala-Va11- P Ala-His-Ala-Nle-NH2-A印a-(Doc)4-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2
_ (Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Ala-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala_Val- P Ala-His-Ala-Nle-NH2 - (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -A印a- (Doc) 2-Gln-Trp-Ala_Val- P Ala-His-Ala-Nle-NH2 _Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:
-Aepa—N. H
pGlu-His-Trp-Ser-Tyr
^"^Leu-Arg-Pro-Gly-NH.
pGlu-His-Trp-Ser-Tyr
-廿Leu-Arg-Pro-Gly-N H, H O
pGlu-His-Trp-Ser-Tyr
—[j^Y~ Leu-Arg-Pro-Gly-NH.<formula>formula see original document page 193</formula><formula>formula see original document page 194</formula><formula>formula see original document page 195</formula><formula>formula see original document page 196</formula>

-(Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
TABLE B
-Doc-B
pGlu-His-Trp-Ser-Tyr-^j^"Leu-Arg-Pra-Gly-NH:
-(Doc):
pGlu-His-Trp-Ser-Tyr-N""Y" Leu-Arg-Pro-Gly-NH2
pGlu-His-Trp-Ser-Tyr一W"V"Leu-Arg-Pro-Gly-NH2
H O
墨(Doc)』
pGlu-His-Trp-Ser-Tyr—y^V"Leu-Arg-Pro-Gly-NH2 - (Doc) 4-A印a-Lys-DTyr-DTyr-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 4-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val—Cys)_Thr_NH2 - (Doc)5-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 - (Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val—Cys)_Thr_NH2 - (Doc) 3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2
- (Doc) 2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 -Doc-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 - (A印a) 2-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Val—Cys) _Thr_NH2 - (Doc) 6-A印a-DPhe-cydo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 - (Doc) 5-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 - (Doc) 3-A印a-DPhe-cydo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 - (Doc) 2-A印a-DPhe-cydo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 -Doc-A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 -A印a- (Doc) 4-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 -A印a- (Doc) 3-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 -A印a- (Doc) 2-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 -A印a-Doc-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 - (Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr—Cys)_Thr_NH2 - (Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 -(Doc)5-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 - (Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 - (Doc) 3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr—Cys)_Thr_NH2 - (Doc) 2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 -Doc-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 - (A印a) 2-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 - (Doc) 6-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 -(00。)5^印&-0 116-。7。10(〇78-31171-011"-1^8-1111-〇78)-1111~^112 - (Doc) 4-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Thr—Cys) _Thr_NH2 - (Doc) 3-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 - (Doc) 2-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 -Doc-A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 -A印a- (Doc) 4-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Thr—Cys) _Thr_NH2 -A印a- (Doc) 3-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 -A印a- (Doc) 2-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Thr—Cys) _Thr_NH2 -A印a-Doc-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 -(00。)4^印&-0 116-。7。10(〇78-31丁71-011"-1^8-1111-〇78)-1111~^112 -(Doc)6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -(Doc)5-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -(Doc)4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -(Doc)3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 - (Doc) 2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -Doc-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2[1019] -(A印a)2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr-NH2 - (Doc) 6-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -(00。)5^印&-0 116-。7。10(〇78-31171-011"-1^8^1311-〇78)-1111~^112 - (Doc) 4-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 3-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 2-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -Doc-A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a- (Doc) 4-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a- (Doc) 3-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a- (Doc) 2-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a-Doc-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr_NH2 - (Doc) 4-A印a-DPhe-cydo (Cys-3ITyr-DTrp-Lys-Val—Cys) _Thr_NH2 - (Doc) 6-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc)5-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 4-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 3-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 2-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -Doc-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (A印a) 2-DPhe-cyclo (Cys-Tyr-DTrp-Lys—Abu—Cys) _Thr_NH2 - (Doc) 6-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) s-A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 3-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 2-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -Doc-A印a-DPhe-cycl0 (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2 _ (Doc) 6_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc)5_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 4_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 3_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 2_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Doc_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Doc_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 - (Doc) 2-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 _ (Doc) 3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _(Doc)5_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2[1058] _ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -A印a- (Doc) 3-DPhe_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a- (Doc) 2-DPhe_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a-Doc-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Th r_NH2 _Aepa_ (Doc) 4_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH: _Aepa_ (Doc) 3_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH: _Aepa_ (Doc) 2_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH: _Aep3_Doc_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -A印a-DP he-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 4-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 _ (A印a) 2-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 _ (Doc) 6-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 _ (Doc) 5-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 _ (Doc) 4-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 _ (Doc) 3-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 _ (Doc) 2-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 -Doc-A印a-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 _ (Doc) 6-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 _ (Doc) 5-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 _ (Doc) 4-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 _ (Doc) 3-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 _ (Doc) 2-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 -Doc-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 -A印a-Doc-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 -A印a- (Doc) 2_Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 -A印a- (Doc) 3_Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 —A印a— (Doc) 4_Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 _ (Doc) 6_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 4_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: -A印a- (Doc) 4-DPhe_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 2-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -(00。)4^印&-0 116-。7。10(〇78-171-011卬-1^8^1311-〇78)-1111~^112 - (Doc) 6-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (A印a) 2-DPhe_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 2-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 4-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 6-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2
199[1097] [1098] [1099] [1100] [1101] [1102] [1103] [1104] [1105] [1106] [1107] [1108] [1109] [川0] [川1] [川3] [川4] [川5] [1116] [川7] [川8] [1119] [1120] [1121] [1122] [1123] [1124] [1125] [1126] [1127] [1128] [1129] [1130]
_ (Doc) 8_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2<formula>formula see original document page 200</formula>
-(A印a) HSDAVFTDNYTRLRKQMAVKKLLNS ILN-NH2
-(A印a) HSDAVFTDNYTRLRKQMAVKKALNS ILN-NH2
-(A印a) HSDAVFTDNYTRLRKQMAVKKFLNS ILN-NH2
-(A印a) HSDAVFTDNYTRLRKQMAVKKYLNS ILN-NH2
-(A印a) HSDAVFTDNYTRLRKQ (Nle) AVKKYLNSILN_NH2
-HSDAVFTDNYTRLRKQMAVKKLLNSILN_NH2
-HSDAVFTDNYTRLRKQMAVKKALNSILN_NH2
-HSDAVFTDNYTRLRKQMAVKKFLNSILN_NH2
-HSDAVFTDNYTRLRKQMAVKKYLNSILN_NH2
-HSDAVFTDNYTRLRKQ(Nle)AVKKYLNSILN_NH2
-Aepa-Caeg-cyclo(DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2
-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2
_ (Doc) 4-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH:
-(A印a) HSDGIFTDSYSRYRKQMA (A5c) KKYLAAVLGKRYKQRVKNK_NH2
-(A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVLGKRYKQR (A6c) KNK_NH2
-(A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVL (Ava) KRYKQRVKNK_NH2
-(A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVL ( P Ala) KRYKQRVKNK_NH2
-HSDGIFTDSYSRYRKQMA(A5c)KKYLAAVLGKRYKQRVKNK_NH2
-HSDGIFTDSYSRYRKQMAVKKYLAAVLGKRYKQR(A6c)KNK_NH2
-HSDGIFTDSYSRYRKQMAVKKYLAAVL(Ava)KRYKQRVKNK_NH2
-HSDGIFTDSYSRYRKQMAVKKYLAAVL(P Ala)KRYKQRVKNK_NH2
_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
_ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:
_ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:
_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2
_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2
_ (Doc) 4_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2
_ (Doc) 6_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2
_Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2
-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2
-(Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2[1131] - (Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 - (A印a) 2-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 _ (A印a) 2_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2 _ (Doc) 6_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 4_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 2_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Aepa_ (Doc) 6_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _Aepa_ (Doc) 4_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH: _ (Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -A印a-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 -Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 _ (Doc) 4-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 _ (Doc) 6-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 -Doc-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Doc-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu-NH2 -Doc-DPhe-G ln—Trp—Ala—Val-PAla—His-Leu-Leu_NH2 -Doc-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Doc-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Doc-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Doc-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle_NH2 -Doc-A印a-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH: -Doc-A印a-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH: -00(;^印&-0 116-6111-11"^1&,&1-617-附8-1^11-1^11^112[1164] -Doc-A印a-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle_NH2 -Doc-A印a-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu-NH2 -A印a-(Doc) 3-DPhe-Gln-Trp-A la-Ala-P Ala-His-Phe-Nle_NH2 -A印a-(Doc)3-DAla-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH2 4印&-(00。)3-0 116-6111-11卬^1&,&1-617-附8-1^11-1^11^112 -A印a-(Doc)3-DPhe-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle_NH2 -A印a- (Doc) 3-DPhe-Gln-Trp-Ala_Val- P Ala-His-Leu-Leu_NH2 - (Doc) 3-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 - (Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH2 - (Doc) 3-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 - (Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle_NH2 - (Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2 -A印a-Doc-DPhe-G ln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 -A印a-Doc-DAla-Gln-Trp-Ala-Val- P Ala_His-Phe-Nle_NH2 4印&-00(3-0 116-6111-11"^1&,&1-617-附8-1^11-1^11^112 -A印a-Doc-DPhe-Gln-Trp-Ala-Val- P Ala_His-Leu_Nle_NH2 -A印a-Doc-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH)-Leu_NH2 - (Doc) 4-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2 -A印a-(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2 - (Doc) 4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W(CH2NH)-Leu_NH2 - (Doc) 4-A印a-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu-NH: -A印a-(Doc)4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu-NH: - (Doc) 4-Gaba-Gln-Trp-Ala-Val-e Ala-His-Leu-Leu_NH2 _(Doc)4_A，_Gaba_Gln_Trp_Ala_Val_e Ala_His_Leu_Leu_NH2 _A，_(Doc)4_Gaba_Gln_Trp_Ala_Val_e Ala_His_Leu_Leu_NH2 -(Doc)4-Gaba-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle-NH2 -(Doc)4-A印a-Gaba-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle-NH2 -A印a-(Doc)4-Gaba-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle_NH2 -A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle_NH2 -A印a-Gln-Trp-Ala-Val-e Ala_His_Leu_Leu_NH2 -A印a-(Doc)2-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle_NH2 -A印a-(Doc)2-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH2 -A印a- (Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -A印a-(Doc)2-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle_NH2 -A印a-(Doc) 2-Gln-Trp-Ala-Val-e Ala-His-Leu-Leu_NH2 -(Doc)2-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -(Doc)2-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH21203] -(Doc)2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2
1204] -(Doc)2-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle-NH2
1205] _(Doc)2_Gln_Trp_Ala_Val_e Ala_His_Leu_Leu_NH2
1206] -A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2
1207] -A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2
1208] -(00(3)4^印&-0 116-6111-11卬^1&,&1-617-附8-1^11-1^11^112
1209] -(Doc)4-A印a-DPhe-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle-NH:
1210] - (Doc) 4-A印a-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu-NH:
1211] -A印a-(Doc)4-DPhe-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle-NH:
1212] -A印a-(Doc)4-DAla-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH:
1213] 4印&-(00(3)4-0 116-6111-11卬^1&,&1-617-附8-1^11-1^11^112
1214] -A印a-(Doc)4-DPhe-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle-NH:
1215] -A印a-(Doc) 4-DPhe-Gln-Trp-Ala-Val-e Ala-His-Leu-Leu-NH:
1216] -(Doc)4-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2
1217] -(Doc)4-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2
1218] -(Doc)4-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2
1219] -(Doc)4-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2
1220] - (Doc) 4-DPhe-Gln-Trp-Ala-Val-e Ala-His-Leu-Leu_NH2
1221] -(Doc)4-A印a-DPhe-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle-NH:
1222] -(Doc)4-A印a-DAla-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH:
1223] _(Doc)4_A，_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2
1224] -(Doc)4-A印a-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle_NH2
1225] _(Doc)4_A，_Gln_Trp_Ala_Val_e Ala_His_Leu_Leu_NH2
1226] -A印a-(Doc)4-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle_NH2
1227] -A印a-(Doc)4-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH2
1228] _A，_(Doc)4_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2
1229] -A印a-(Doc)4-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle_NH2
1230] _A，_(Doc)4_Gln_Trp_Ala_Val_e Ala_His_Leu_Leu_NH2
1231] -(Doc)4-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2
1232] -(Doc)4-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2
1233] -(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2
1234] -(Doc)4-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle-NH2
1235] _(Doc)4_Gln_Trp_Ala_Val_e Ala_His_Leu_Leu_NH2
1236] -(Doc)4-A印a-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle_NH2
1237] -(Doc)4-A印a-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH2
1238] -A印a-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2
1239] -A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2
1240] - (Doc) 2-DPhe-Gln-Trp-Ala-Val-e Ala-His-Leu-Leu_NH2
1241] - (Doc) 2-DPhe-Gln-Trp-Ala-Val-eAla-His-Leu-N le_NH2[1242] -(Doc)2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 [1243] -(Doc)2-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH: [1244] -(Doc)2-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH: -A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 -A印a-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -(Doc)2-A印a-DPhe-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle-NH: -(Doc)2-A印a-DAla-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH: -(00。)2^印&-0 116-6111-11卬^1&,&1-617-附8-1^11-1^11^112 -(Doc)2-A印a-DPhe-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle-NH: - (Doc) 2-A印a-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu-NH: -A印a-(Doc)2-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -(Doc)2-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a-(Doc)2-DPhe-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH: -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -(Doc)2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Ala-Nle-NH2 -A印a-(Doc)4-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc)2-A印a-DPhe-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH: -(Doc)2-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 - (Doc) 4-DPhe-G ln—Trp—A la—Va 1_PAla-His-Ala-Nle-NH2 -(Doc)4-A印a-DPhe-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH: -A印a-(Doc)4-DPhe-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH: -(Doc)4-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc)4-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 _A，_Doc_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2 -A印a-Doc-Gln-Trp-Ala-Val- P Ala_His-Leu_Nle_NH2 [1246]
TABLE C[1275] -A印a-Doc-Gln-Trp-Ala-Val- P Ala-His_Leu_Leu_NH2 -A印a-(Doc)3-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle_NH2 -A印a-(Doc)3-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH2 4印&-(00。)3-6111-11卬41&,&1-617-附8-1^11-1^11^112 -A印a-(Doc)3-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle_NH2 -A印a-(Doc) 3-Gln-Trp-Ala-Val-e Ala-His-Leu-Leu_NH2 -(Doc)3-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -(Doc)3-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -(Doc)3-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -(Doc)3-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle-NH2 _ (Doc) 3_Gln_Trp_Ala_Val_P Ala-His_Leu_Leu_NH2 -A印a-Doc-Gln-Trp-Ala-Ala- P Ala_His-Phe-Nle_NH2 -A印a-Doc-Gln-Trp-Ala-Val- P Ala_His-Phe-Nle_NH2 -(00。)3^印&-0 116-6111-11卬^1&,&1-617-附8-1^11-1^11^112 -(Doc)3-A印a-DPhe-Gln-Trp-Ala-Val-e Ala-His-Lau-Nle-NH: - (Doc) 3-A印a-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu-NH: -(Doc)3-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -(Doc)3-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -(Doc)3-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc)3-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 - (Doc) 3-DPhe-Gln-Trp-Ala-Val-e Ala-His-Leu-Leu_NH2 -Doc-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Doc-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -Doc-A印a-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle_NH2 -Doc-A印a-Gln-Trp-Ala-Val- P Ala_His-Phe-Nle_NH2 _Doc_A，_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2 -Doc-A印a-Gln-Trp-Ala-Val- P Ala_His-Leu_Nle_NH2 -Doc-A印a-Gln-Trp-Ala-Val- P Ala-His_Leu_Leu_NH2 [1306]<formula>formula see original document page 206</formula><formula>formula see original document page 207</formula><formula>formula see original document page 208</formula><formula>formula see original document page 209</formula><formula>formula see original document page 210</formula>OJOAO-^dcI-"(。08- 〔62￡
NHNJyu- (SA3-I13>-SAJ-d.!J,CI-.!AJJ￡-SA3) 0J。A0-①IKCH3d①v」(。081 〔93￡
NHNJyu- (SA3-I13>-SAJ-d.!J,CI-.!AJJ￡-SA3) 0J。A0-①IKCH3d①v」(。081 〔寸3￡
NHNJyu- (SA3-I13>-SAJ-d.!J,CI-.!AJJ￡-SA3) 0J。A0-①IKCH3d①v」(。081 〔￡3￡
NHNJyu- (SA3-I13>-SAJ-d.!J,CI-.!AJJ￡-SA3) 0J。A0-①IKCH3d①v」(。081 〔32￡
NHNJyu-(s^:l-I13i\-SAJ-d.!J,CI-.!AJJ￡-SA3)OJ。AO-^dcH3&v」(。08- 〔9l￡
NHNJyu- (SA3-nqv-SAJ-dJJ,a-.!AVSA3) 0J。A。-①Iya-13d①v」(。oa) I 〔w￡
NHNJyu- (SA3-nqv-SAJ-dJJ,a-.!AVSA3) 0PA。-^da-13&v- 〔21￡
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fj — f 丫
o H
"ie d- n91,vz—」Al-」as-d」l-s!工-n一9d[1331] -A印a-(Doc)4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr-NH2 —A印a-(Doc)3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr-NH2 —A印a-(Doc)2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr-NH2 -A印a-Doc-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 -(Doc)6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)-Thr_NH2 -(Doc)5-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)-Thr_NH2 -(Doc)4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)-Thr_NH2 -(Doc)3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)-Thr_NH2 -(Doc)2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)-Thr_NH2 -Doc-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 -(A印a)2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)-Thr-NH2 -(00。)6^印&-0 116-。7。10(〇78-31丁71-011"-1^8-1111-〇78)-1111~^112 -(00。)5^印&-0 116-。7。10(〇78-31171-011"-1^8-1111-〇78)-1111~^112 -(00。)3^印&-0 116-。7。10(〇78-31171-011"-1^8-1111-〇78)-1111~^112 -(00。)2^印&-0 116-。7。10(〇78-31丁71-011"-1^8-1111-〇78)-1111~^112 -Doc-A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 ^印&-(00。)4-0 116-。7。10(〇78-31171-011"-1^8-1111-〇78)-1111~^112 ^印&-(00。)3-0 116-。7。10(〇78-31丁71-011"-1^8-1111-〇78)-1111~^112 ^印&-(00。)2-0 116-。7。10(〇78-31丁71-011"-1^8-1111-〇78)-1111~^112 -A印a-Doc-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 -(00。)4^印&-0 116-。7。10(〇78-31171-011"-1^8-1111-〇78)-1111~^112 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 -(Doc)4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)-Thr_NH2 -(Doc)6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)-Thr_NH2 -(Doc)6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -(Doc)5-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -(Doc)4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -(Doc)3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -(Doc)2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -Doc-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -(A印a)2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr-NH2 - (Doc) 6-A印a-DP he-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr-NH: -(00。)5^印&-0 116-。7。10(〇78-31丁71-011"-1^8^1311-〇78)-1111~^112 -(00。)3^印&-0 116-。7。10(〇78-31171-011"-1^8^1311-〇78)-1111~^112 -(00。)2^印&-0 116-。7。10(〇78-31171-011"-1^8^1311-〇78)-1111~^112 -Doc-A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2[1370] ^印&-(00。)4-0 116-。7。10(〇78-31171-011"-1^8^1311-〇78)-1111~^112 ^印&-(00。)3-0 116-。7。10(〇78-31171-011"-1^8^1311-〇78)-1111~^112 ^印&-(00。)2-0 116-。7。10(〇78-31丁71-011"-1^8^1311-〇78)-1111~^112 -A印a-Doc-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -(00。)4^印&-0 116-。7。10(〇78-31丁71-011"-1^8^1311-〇78)-1111~^112 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -(Doc)4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -(Doc)6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -(Doc)6-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr_NH2 - (Doc) 5-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 4-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 3-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -(Doc)2-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -Doc-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (A印a) 2-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 6-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) s-A印a-DP he-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 3-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -(00。)2^印3-0 116-。7。10(〇78-171-011卬-1^8^1311-〇78)-1111~^112 -Doc-A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (A印a) 2-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 6-A印a-Lys-DTyr-DTyr-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) -Thr-NH: _ (Doc) 5_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 4_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 3_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: - (Doc) 2-A印a-Lys-DTyr-DTyr-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) -Thr-NH: _Doc_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -(Doc)4-A印a-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH2 - (Doc) 4-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 - (Doc) 4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle_NH2 - (Doc) 4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2 -A印a-(Doc)4-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle_NH2 -A印a- (Doc) 4-Gln-Trp-Ala_Val- P Ala-His-Phe-Nle_NH2 -A印a- (Doc) 4-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -A印a- (Doc) 4-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle_NH2
2131409]—Aepa--(Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2
1410]-(Doc)4-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2
1411]-(Doc)4-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2
1412]-(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2
1413]-(Doc)4-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2
1414]-(Doc)4-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2
1415]-(Doc)4-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2
1416]-(Doc)6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
1417]-(Doc)5_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
1418]-(Doc)4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
1419]-(Doc)3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
1420]-(Doc)2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
1421]_Doc_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH21422]—Aepa--(Doc) 4_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
1423]—Aepa--(Doc) 3_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
1424]—Aepa--(Doc) 2_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
1425]—Aepa--Doc_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
1426]—Aepa--(Doc) 4_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
1427]—Aepa--(Doc) 3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
1428]—Aepa--(Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
1429]—Aepa--Doc_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
1430]-(Doc)6_Aep3_Caeg_cyclo (DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2
1431]-(Doc)4_Aep3_Caeg_cyclo(DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2
1432]—Aepa--Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2
1433]_Caeg--cyclo(DCys-3Pal-DTrp-Lys-DCys)-Thr(Bzl)_Tyr_NH2
1434]-(Doc)4-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2
1435]-(Doc)6-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2
1436]_ (A印a) 2-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH21437]-(Doc)6_Aep3_Caeg_cyclo (DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2
1438]-(Doc)5_Aep3_Caeg_cyclo (DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2
1439]-(Doc)4_Aep3_Caeg_cyclo(DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2
1440]-(Doc)3_Aep3_Caeg_cyclo(DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2
1441]-(Doc)2_Aep3_Caeg_cyclo (DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2
1442]_Doc_Aep3_Caeg_cyclo(DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH21443]-(Doc)6-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2
1444]-(Doc)5-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2
1445]-(Doc)4-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2
1446]-(Doc)3-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2
1447]-(Doc)2-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2[1448] -Doc-Caeg-cyclo(DCys-3Pal-DTrp-Lys-DCys)-Thr(Bzl)_Tyr_NH2 -A印a- (Doc) 4_Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH: -A印a- (Doc) 3_Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH: —A印a— (Doc) 2_Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH: -A印a-Doc-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 [1453] -A印a- (Doc) 2_Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH: -A印a-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 -Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 -A印a- (Doc) 2-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 - (Doc) 4-A印a-DPhe-cydo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 -DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 [1461] _Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 4-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH: _ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: [1466]
O -A印a- (Doc) 2_Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH: [1468] -A印a-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 [1469] -Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 [1470] -A印a- (Doc) 2-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 [1471] -(Doc)4-A印a-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr-NH2CN [1472] -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val—Cys) —Thr—NH: -DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 TABLE D [1475]
O_(Doc)2--Gln--Trp--Ala--Ala--PAla-His-Phe-Nle-NH2_(Doc)2--Gln--Trp--Ala--Val--PAla-His-Phe-Nle-NH2_(Doc)2--Gln--Trp--Ala-val--Gly-His-Leu-Leu-NH2_(Doc)2--Gln--Trp--Ala--Val--PAla-His-Leu-Nle-NH2_(Doc)2--Gln--Trp--Ala--Val-Ala-His-Leu-Leu-NH2 -A印a-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle_NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2 -A印a-Gln-Trp-Ala-Val- P Ala_His_Leu_Leu_NH2 -A印a-(Doc)2-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle-NH: -A印a- (Doc) 2-Gln-Trp-Ala_Val- P Ala-His-Phe-Nle-NH: -A印a- (Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -A印a- (Doc) 2-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle-NH: -A印a- (Doc) 2-Gln-Trp-Ala_Val- P Ala-His-Leu-Leu-NH: -(Doc)2-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -(Doc)2-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 - (Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 - (Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 - (Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -A印a-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-N H2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-叫 -A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2 -A印a—Gln—Trp—Ala—Val- P Ala_His_Leu_Leu_NH2—Aepa—(Doc)2--Gln--Trp--Ala--Ala--eAla--His--Phe--Nle--NH2—Aepa—(Doc)2--Gln--Trp--Ala--Val--PAla--His--Phe--Nle--NH2—Aepa—(Doc)2--Gln--Trp--Ala-val--Gly-His-Leu-Leu-NH2[1504]—Aepa—(Doc)2--Gln--Trp--Ala--Val--eAla--His--Leu--Nle--NH2—Aepa—(Doc)2--Gln--Trp--Ala-val--PAla--His--Leu--Leu--NH2—Aepa—(Doc)2--Gln--Trp--Ala--Val--eAla--His--Leu--Leu-—NH2
2161507]-(Doc)4-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2
1508]-(Doc)4-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2
1509]-(Doc)4-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2
1510]-(Doc)4-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2
1511]-(Doc)4-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2
1512]-(Doc)4-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle--NH2
1513]-(Doc)4-A印a-DAla-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle--NH2
1514]-(Doc)4-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH21515]-(Doc)4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle--NH2
1516]-(Doc)4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu--NH2
1517]—Aepa--(Doc) 4-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle--NH2
1518]—Aepa--(Doc) 4-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle--NH2
1519]—Aepa--(Doc) 4-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH21520]—Aepa--(Doc) 4-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle--NH2
1521]—Aepa--(Doc) 4-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu--NH2
1522]-(Doc)4-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2
1523]-(Doc)4-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2
1524]-(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2
1525]-(Doc)4-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2
1526]-(Doc)4-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2
1527]-(Doc)4-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2
1528]-(Doc)4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH2
1529]-(Doc)4_Aepa_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2
1530]-(Doc)4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH2
1531]-(Doc)fA印a-Gln-Trp-Ala-Val- P Ala_His_Leu_Leu_NH2
1532]—Aepa--(Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2
1533]—Aepa--(Doc)4-Gln-Trp-Ala-Ala-PAla-His-Phe-Nle-NH2
1534]—Aepa--(Doc) 4-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2
1535]—Aepa--(Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2
1536]—Aepa--(Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2
1537]—Aepa--(Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu--NH2
1538]—Aepa--(Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle--NH2
1539]—Aepa--(Doc) 2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH21540]—Aepa--(Doc) 2-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle--NH2
1541]—Aepa--(Doc) 2-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle--NH2
1542]—Aepa--DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2
1543]—Aepa--DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2
1544]—Aepa--DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2
1545]—Aepa--DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2[1546] [1547] [1548] [1549] [1550] [1551] [1552] [1553] [1554] [1555] [1556] [1557] [1558] [1559] [1560] [1561] [1562] [1563] [1564] [1565] [1566] [1567] [1568] [1569] [1570] [1571] [1572] [1573] [1574] [1575] [1576] [1577] [1578] [1579] [1580] [1581] [1582] [1583]
-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -(Doc) 2-DPhe-Gl n-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 2-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2 -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH2 -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2
-NH2 -NH9
-NH9
-(Doc) 2-A印a-DAla-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle--(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle--A印a- (Doc)2-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -(Doc)2-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle--A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Ala-Nle-NH2 -A印a- (Doc)4-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc)4-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc)4-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle--(Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle--(Doc)4-DPhe-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -(Doc)2-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle--Aepa- (Doc) 4_Gaba_Gln_Trp_Ala_Val_ P Ala-His-Leu-Leu--(Doc) 4_Aepa_Gaba_Gln_Trp_Ala_Val_ P Ala-His-Leu-Leu--A印a-(Doc)4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2 -(Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc) 4-A印a-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2 -(Doc)4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2N H)-Leu_NH2 -A印a-(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2 -(Doc) 4-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2 -(Doc) 4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2 -A印a- (Doc) 4_Gaba_Gln_Trp_Ala_Val_ P Ala_His_Leu_Nle_NH2 -(Doc) 4-A印a-Gaba-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle_NH2 -(Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2
-NH2 -NH。
-NH2 -NH2 -NH9<formula>formula see original document page 219</formula>-A印a-Doc — N-H
pGlu-His-Trp-Ser-Tyr—N^YLeu-Arg-Pro-Gly-NH2
-Aepa-(Doc)2 一乜
pGlu-His-Trp-Ser-Tyr_3^pLeu-Arg-Pro-Gly-NH2
O
-Aepa-(Doc)3 — N-H
pGlu-His-Trp-Ser-Tyr — 口'
-Leu-Arg-Pro-Gly-NH2
O
-Aepa-(Doc)4—N-H
pGlu-His-Trp-Ser-Tyr一^^pLeu-Arg-Pro-Gly-NH2
H O
-Aepa — N— H
pGlu-His-Trp-Ser-Tyr —
H
-Leu-Arg-Pro-Gly-NH2
O
-(Doc)2-Aepa—N-H
pGlu-His-Trp-Ser-Tyr — N'
H
-Leu-Arg-Pro-Gly-NH2
O
-(Doc)3-Aepa —N-H
pGlu-His-Trp-Ser-Tyr -^j ^Y"Leu-Arg-Pro-Gly-NH2
0
-(Doc)4-Aepa—N-H
pGlu-His-Trp-Ser-Tyr—N"^Y""Leu-Arg-Pro-Gly-NH2<formula>formula see original document page 221</formula><formula>formula see original document page 222</formula><formula>formula see original document page 223</formula><formula>formula see original document page 224</formula> -HSDGIFTDSYSRYRKQMAVKKYLAAVL(P Ala)KRYKQRVKNK_NH2 -HSDGIFTDSYSRYRKQMAVKKYLAAVL(Ava)KRYKQRVKNK_NH2 -HSDGIFTDSYSRYRKQMAVKKYLAAVLGKRYKQR (A6c) KNK_NH2 -HSDGIFTDSYSRYRKQMA (A5c) KKYLAAVLGKRYKQRVKNK_NH2 - (A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVL ( P Ala) KRYKQRVKNK_NH2 - (A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVL (Ava) KRYKQRVKNK_NH2 - (A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVLGKRYKQR (A6c) KNK_NH2 - (A印a) HSDGIFTDSYSRYRKQMA (A5c) KKYLAAVLGKRYKQRVKNK_NH2 -A印a-Doc-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 -A印a- (Doc) 2_Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH: -A印a- (Doc) 3_Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH: -A印a- (Doc) 4_Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH: -(Doc)6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr_NH2 -(Doc)4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr_NH2 -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 —(Doc)4-A印a-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr-NH2 -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 -Doc-A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 —(Doc)2-A印a-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr-NH2 - (Doc) 3—A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val—Cys) _Thr_NH2 - (Doc) s-A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val—Cys) _Thr_NH2 —(Doc)6-A印a-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr-NH2[1613] -(A印a)2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr-NH2 -Doc-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr_NH2 -(Doc)2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr_NH2 -(Doc)3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr_NH2 - (Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val—Cys)_Thr_NH2 -(Doc)5-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr_NH2 -(Doc)6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr_NH2 -A印a-Doc-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 —A印a-(Doc)2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr-NH2 —A印a-(Doc)3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr-NH2 -A印a-(Doc)4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr-NH2 -Doc-A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 -(00。)2^印&-0 116-。7。10(〇78-31丁71-011"-1^8-1111-〇78)-1111~^112 -(00。)3^印&-0 116-。7。10(〇78-31丁71-011"-1^8-1111-〇78)-1111~^112 -(00。)5^印&-0 116-。7。10(〇78-31171-011"-1^8-1111-〇78)-1111~^112 -(00。)6^印&-0 116-。7。10(〇78-31丁71-011"-1^8-1111-〇78)-1111~^112 -(A印a)2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)-Thr-NH2 -Doc-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 -(Doc)2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)-Thr_NH2 -(Doc)3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)-Thr_NH2 -(Doc)4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)-Thr_NH2 -(Doc)5-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)-Thr_NH2 -(Doc)6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)-Thr_NH2 -A印a-Doc-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 ^印&-(00。)2-0 116-。7。10(〇78-31171-011"-1^8-1111-〇78)-1111~^112 ^印&-(00。)3-0 116-。7。10(〇78-31丁71-011"-1^8-1111-〇78)-1111~^112 ^印&-(00。)4-0 116-。7。10(〇78-31丁71-011"-1^8-1111-〇78)-1111~^112 -(Doc)6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)-Thr_NH2 -(Doc)4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)-Thr_NH2 -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 -(00。)4^印&-0 116-。7。10(〇78-31171-011"-1^8-1111-〇78)-1111~^112 -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Thr—Cys) _Thr_NH2 -Doc-A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -(00。)2^印&-0 116-。7。10(〇78-31丁71-011"-1^8^1311-〇78)-1111~^112 -(00。)3^印&-0 116-。7。10(〇78-31丁71-011"-1^8^1311-〇78)-1111~^112 -(00。)5^印&-0 116-。7。10(〇78-31171-011"-1^8^1311-〇78)-1111~^112 -(00。)6^印&-0 116-。7。10(〇78-31171-011"-1^8^1311-〇78)-1111~^112[1652] -(A印a)2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr-NH2 -Doc-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -(Doc)2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -(Doc)3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -(Doc)4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -(Doc)5-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -(Doc)6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -A印a-Doc-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 ^印&-(00。)2-0 116-。7。10(〇78-31171-011"-1^8^1311-〇78)-1111~^112 ^印&-(00。)3-0 116-。7。10(〇78-31171-011"-1^8^1311-〇78)-1111~^112 ^印&-(00。)4-0 116-。7。10(〇78-31丁71-011"-1^8^1311-〇78)-1111~^112 -(Doc)6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -(Doc)4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -(00。)4^印&-0 116-。7。10(〇78-31171-011"-1^8^1311-〇78)-1111~^112 -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 _Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -(Doc)4-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -(Doc)6-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr_NH2 - (Doc) 4-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (A印a) 2_ (Doc) 2-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -Aepa-Doc-Aepa-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -(A印a)2-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2 -(Doc)2-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr_NH2 - (A印a) 2_ (Doc) 4_DPhe_cyclo (Cys-Tyr-DTrp-Lys—Abu—Cys) _Thr_NH2 -A印a- (Doc) 6-DPhe_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -(00。)2^印3-0 116-。7。10(〇78-171-011卬-1^8^1311-〇78)-1111~^112 -A印a- (Doc) 4_A，_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH: - (Doc) 6-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 2_ (A印a) 2-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 _Doc_Aepa_DPhe_cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 2-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 3-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) s-A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 6-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (A印a) 2-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2
226[1691] -Doc-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2 -(Doc)2-DPhe-cycl。(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2 - (Doc) 3-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 4-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 5-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -(Doc)6-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2 _Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Doc_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 2_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 3_Aepa_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 4_Aepa_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 5_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 6_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH: _ (Aepa) 2_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Doc_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2 - (Doc) 4-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 5-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 _ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Aepa_Doc_Lys__DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -Aepa- (Doc) 2_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH: -Aepa- (Doc) 3_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH: -Aepa- (Doc) 4_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH: _Aepa_Doc_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -A印a- (Doc) 2_DPhe_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a- (Doc) 3-DPhe_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a- (Doc) 4_DPhe_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 [1719]-Aepa — N-H
pGlu-His-Trp-Ser-Tyr — N^pLeu-Arg-Pro-Gly-NI^
-(Doc)2-Aepa—N H
pGlu-His-Trp-Ser-Tyr—^j、Leu-Arg-Pro-Gly-NH2
H
O
-(Doc)4-Aepa — N-H
pGlu-His-Trp-Ser-Tyr — fj^YLeu-Arg-Pro-Gly-NH2<formula>formula see original document page 229</formula><formula>formula see original document page 230</formula><formula>formula see original document page 231</formula><formula>formula see original document page 232</formula>
<formula>formula see original document page 232</formula>
<formula>formula see original document page 232</formula>[1724] _Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -Lys-Lys-Lys-DTyr-DTyr-cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Aepa_ (Doc) 4_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2 - (Doc) 2-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 4-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 6-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 8-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 _Aepa_ (Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 - (A印a) 2-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 _ (Doc) 2_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 4_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 6_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Aepa_ (Doc) 2_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2 _Aepa_ (Doc) 4_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2 _Aepa_(Doc)6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -Lys-Aepa-Lys-DTyr-DTyr-cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2[1742] -DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -A印a-Lys-DTyr-DTyr- (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 2-A印a-Lys-DTyr-DTyr- (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a- (Doc) 2-A印a-Lys-DTyr-DTyr- (Cys-Tyr-DTrp-Lys-Abu-Cys) -Thr-NH: - (Doc) 6-A印a-Lys-DTyr-DTyr- (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 _Doc_Aep3_Doc_Aepa_DPhe_cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 4-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -Doc-A印a-Lys-DTyr-DTyr- (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 2-A印a-Lys-DTyr-DTyr- (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 3-A印a-Lys-DTyr-DTyr- (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 4-A印a-Lys-DTyr-DTyr- (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -Aepa-Doc-Aepa-Lys-DTyr-DTyr-(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Doc_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 [1757] _ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: [1759] _Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 [1761]
TABLE E
233[1762] _ (Doc) 6-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 _ (Doc) 4-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 -Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 -A印a-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 _ (Doc) 4-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH: _ (Doc) 6-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH: -Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 -A印a-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 -Doc-A印a-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 -(Doc)2-A印a-Caeg-cyclo(DCys-3Pal-DTrp-Lys-DCys)-Thr(Bzl)-Tyr-NH: _ (Doc) 3-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH: _ (Doc) 4-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH: _ (Doc) s-A印a-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH: _ (Doc) 6-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH: _ (A印a) 2-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 -Doc-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 _ (Doc) 2-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 _ (Doc) 3-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 _ (Doc) 4-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 _ (Doc) 5-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 _ (Doc) 6-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 - (A印a) 2_ (Doc) 2-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -Aepa-Doc-Aepa-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (A印a) 2-DPhe-cyclo (Cys-Tyr-DTrp-Lys—Abu—Cys) _Thr_NH2 _Doc_Aep3_Doc_Aepa_DPhe_cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 2-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (A印a) 2_ (Doc) 4-DPhe_cyclo (Cys-Tyr-DTrp-Lys—Abu—Cys) _Thr_NH2 ^印&-(00。)6-0 116-。7。10(〇78-171-011卬-1^8^1311-〇78)-1111~^112 -(00。)2^印3-0 116-。7。10(〇78-171-011卬-1^8^1311-〇78)-1111~^112 -A印a- (Doc) 4_A，_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2 -(00。)6^印&-0 116-。7。10(〇78-171-011卬-1^8^1311-〇78)-1111~^112 - (Doc) 2_ (A印a) 2-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -HSDAVFTDNYTRLRKQ(Nle)AVKKYLNSILN_NH2 -HSDAVFTDNYTRLRKQMAVKKYLNSILN-NH2 -HSDAVFTDNYTRLRKQMAVKKFLNSILN-NH2 -HSDAVFTDNYTRLRKQMAVKKALNSILN-NH2 -HSDAVFTDNYTRLRKQMAVKKLLNSILN-NH2 - (A印a) HSDAVFTDNYTRLRKQ (Nle) AVKKYLNSILN_NH2 - (A印a) HSDAVFTDNYTRLRKQMAVKKYLNSILN-NH2[1801] [1802] [1803] [1804] [1806] [1807] [1808] [1809] [1810] [1811] [1812] [1813] [1814] [1815] [1816] [1817] [1818] [1819] [1821] [1822]
H2 [1824]
-(A印a) HSDAVFTDNYTRLRKQMAVKKFLNS ILN-NH2 -(A印a) HSDAVFTDNYTRLRKQMAVKKALNS ILN-NH2 -(A印a) HSDAVFTDNYTRLRKQMAVKKLLNS ILN-NH2
-DTrp-Lys-Abu-Cys)_Thr_NH2 -Lys-Abu-Cys)_Thr_NH2 -Lys-Abu-Cys)_Thr_NH2 -Lys-Abu-Cys)_Thr_NH2 -Lys-Abu-Cys)_Thr_NH2 -DTrp-Lys-Abu-Cys)_Thr_NH2
_Aepa_ (Doc) 4_Lys_DTyr_DTyr_cyclo (Cys_Tyr--(Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp--(Doc) 4_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp--(Doc) 6_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp--(Doc) 8_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp-_Aepa_ (Doc) 2_Lys_DTyr_DTyr_cyclo (Cys_Tyr--(A印a) 2_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2 -(Doc) 2_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -(Doc) 4_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -(Doc) 6_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Aepa_ (Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Aepa_ (Doc) 4_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Aepa_ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -Lys_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
-Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
-(Doc) 2_Aep3_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
-Aepa- (Doc) 2_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_N
-(Doc) 6_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2[1825] [1826] [1827] [1828] [1829] [1830] [1832] [1833] [1834] [1835] [1836] [1837] [1838] [1839] [1840] [1841] [1842] [1843] [1844] [1845] [1846] [1847] [1848] [1849] [1850] [1851] [1852] [1853] [1854] [1855] [1856] [1857]
_ (Doc) 2_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Doc_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 3_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 4_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Aep3_Doc_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)-Thr-NH:
-Doc-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -Doc-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Doc-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Doc-DAla-Gln-Trp-Ala-Var-P Ala-His-Phe-Nle-NH2 -Doc-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -Doc-A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -Doc-A印a-DPhe-Gln-Trp-Ala-Val- P Ala_His-Leu_Nle_NH2
-Doc-A印a-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -Doc-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 -A印a- (Doc) 3-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu-NH: -A印a- (Doc) 3-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH: -A印a- (Doc) 3-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a- (Doc) 3-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH: -A印a- (Doc) 3-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH: -(Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2 -(Doc) 3-A印a-Gln-Trp-Ala-Va 1- P Ala-His-Leu-Nle-NH2 -(Doc) 3-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH2 -(Doc) 3-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -A印a-Doc-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -A印a-Doc-DPhe-Gln-Trp-Ala-Val- P Ala_His-Leu_Nle_NH2
-A印a-Doc-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-Doc-DPhe-Gln-Trp-A la-Ala- P Ala-His-Phe-Nle_NH2 -A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2[1858] 4印&-(00。)2-6111-11卬41&,&1-617-附8-1^11-1^11^112 -A印a-(Doc)2-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle_NH2 -A印a-(Doc)2-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle_NH2 -A印a-Gln-Trp-Ala-Val-e Ala_His_Leu_Leu_NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2 -A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle_NH2 -Aepa-(Doc) 2-Gln-Trp-Ala-Val_e Ala-His-Leu-Leu_NH2 -A印a-(Doc)2-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle_NH2 4印&-(00。)2-6111-11卬41&,&1-617-附8-1^11-1^11^112 —A印a-(Doc)2-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle_NH2 -A印a-(Doc)2-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle_NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -A印a-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 _ (Doc) 2_Gln_Trp_Ala_Val_P Ala-His_Leu_Leu_NH2 -(Doc)2-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle-NH2 -(Doc)2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc)2-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -(Doc)2-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -A印a-(Doc)4-Gaba-Gln-Trp-Ala-Val-e Ala_His_Leu_Leu_NH2 -(Doc)4-A印a-Gaba-Gln-Trp-Ala-Val-e Ala_His_Leu_Leu_NH2 - (Doc) 4-Gaba-Gln-Trp-Ala-Val-e Ala-His-Leu-Leu_NH2 -A印a-(Doc)4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2 - (Doc) 4-A印a-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2 - (Doc) 4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2 -A印a-(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH)-Leu_NH2 -(Doc)4-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH)-Leu_NH2 -(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH)-Leu_NH2 -A印a-(Doc)4-Gaba-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle_NH2 -(Doc)4-A印a-Gaba-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle_NH2 -(Doc)4-Gaba-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle-NH2<formula>formula see original document page 238</formula> [1894] [1895] [1896] [1897] [1898] [1899] [1900] [1901] [1902] [1903] [1904] [1905] [1906] [1907] [1908] [1909] [1910] [1911] [1912] [1913] [1914] [1915] [1916] [1917] [1918] [1919] [1920] [1921] [1922] [1923] [1924] [1925]
<formula>formula see original document page 238</formula>
-Doc-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -Doc-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Doc-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Doc-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Doc-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -(Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -(Doc) 2-Gln-Trp-Ala-Ala- P Ala-His
-A印a'
-A印a'
-A印a'
-A印a'
-A印a'
-(Doc
-(Doc
-(Doc
-(Doc
-(Doc
-(Doc
-(Doc
-(Doc
-(Doc
-(Doc
-A印a-
-A印a-
-A印a-
-A印a-
-A印a-
-(Doc)
-(Doc)
(Doc) 4-DPhe-Gln-Trp-Ala-Val (Doc) 4-DPhe-Gln-Trp-Ala-Val (Doc) 4-DPhe-Gln-Trp-Ala-Val (Doc) 4-DAla-Gln-Trp-Ala-Val (Doc) 4-DPhe-Gln-Trp-Ala-Ala 4-A印a-DPhe-Gln-Trp-Ala-Val 4-A印a-DPhe-Gln-Trp-Ala-Val 4-A印a-DPhe-Gln-Trp-Ala-Val 厂A印a-DAla-Gln-Trp-Ala-Val 厂A印a-DPhe-Gln-Trp-Ala-Ala 4-DPhe-Gln-Trp-Ala-Val 4-DPhe-Gln-Trp-Ala-Val 4-DPhe-Gln-Trp-Ala-Val 4_DA1a_G1n-Trp_A1a_Va1 4-DPhe-Gln-Trp-Ala-Ala (Doc) 4-Gln-Trp-Ala-Val (Doc) 4-Gln-Trp-Ala-Val (Doc) 4-Gln-Trp-Ala-Val (Doc) 4-Gln-Trp-Ala-Val (Doc) 4-Gln-Trp-Ala-Ala 4_Aepa_G1n_Trp_A1a_Va1 4_Aepa_G1n_Trp_A1a_Va1
Phe-Nle_NH2 PAla-His-Leu-Leu-NH2 PAla-His-Leu-Nle-NH2 Gly—His—Leu—Leu—NH2 PAla-His-Phe-Nle-NH2 PAla-His-Phe-Nle-NH2 PAla-His-Leu-Leu-NH2 PAla-His-Leu-Nle-NH2 Gly—His—Leu—Leu—NH2 PAla-His-Phe-Nle-NH2 PAla-His-Phe-Nle-NH2 PAla-His-Leu-Leu-NH2 PAla-His-Leu-Nle-NH2 Gly-His-Leu-Leu-NH2 PAla-His-Phe-Nle-NH2 PAla-His-Phe-Nle-NH2 PAla-His-Leu-Leu-NH2 PAla-His-Leu-Nle-NH2 Gly-His-Leu-Leu-NH2 PAla-His-Phe-Nle-NH2 PAla-His-phe-Nle-NH2 PAla-His-Leu-Leu-NH2 PAla-His-Leu-Nle-NH,[1926] _(Doc)4_A，_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2 -(Doc)4-A印a-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle_NH2 -(Doc)4-A印a-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle_NH2 _ (Doc) 4_Gln_Trp_Ala_Val_P Ala-His_Leu_Leu_NH2 -(Doc)4-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle-NH2 -(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -(Doc)4-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -(Doc)4-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -A印a-(Doc) 2-DPhe-Gln-Trp-Ala-Val-e Ala-His-Leu-Leu-NH: -A印a-(Doc)2-DPhe-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle-NH: 4印&-(00。)2-0 116-6111-11卬^1&,&1-617-附8-1^11-1^11^112 -A印a-(Doc)2-DAla-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH: -A印a-(Doc)2-DPhe-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle-NH: -A印a-DPhe-Gln-Trp-Ala-Val-e Ala_His_Leu_Leu_N H2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2 4印&-0 116-6111-11"^1&,&1-617-附8-1^11-1^11^112 -A印a-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 - (Doc) 2-DPhe-Gln-Trp-Ala-Val-e Ala-His-Leu-Leu_NH2 -(Doc)2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -(Doc)2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -(Doc)2-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -(Doc)2-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 - (Doc) 2-A印a-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu-NH: -(Doc)2-A印a-DPhe-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle-NH: -(00。)2^印&-0 116-6111-11卬^1&,&1-617-附8-1^11-1^11^112 -(Doc)2-A印a-DAla-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH: -(Doc)2-A印a-DPhe-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle-NH: -A印a-(Doc)2-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a-Gln-Trp-Ala-Val-P Ala-His-Ala-Nle-NH2 -(Doc)2-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a-(Doc)2-DPhe-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH: -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -(Doc)2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Ala-Nle-NH2 -A印a-(Doc)4-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc)4-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc)4-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a-(Doc)4-DPhe-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH: -(Doc)4-A印a-DPhe-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH:
239[1965] -(Doc)4-DPhe-Gln-Trp-Ala-Val-P Ala-His-Ala-Nle-NH2 -(Doc)2-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc)2-A印a-DPhe-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH: -A印a-(Doc)3-Gln-Trp-Ala-Val-e Ala_His_Leu_Leu_NH2 -A印a-(Doc)3-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle_NH2 4印&-(00(3)3-6111-11卬41&,&1-617-附8-1^11-1^11^112 -A印a-(Doc)3-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH2 -A印a-(Doc)3-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle_NH2 -A印a-Doc-Gln-Trp-Ala-Val- P Ala-His_Leu_Leu_NH2 -A印a-Doc-Gln-Trp-Ala-Val- P Ala_His-Leu_Nle_NH2 _A，_Doc_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2 -A印a-Doc-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle_NH2 -A印a-Doc-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle_NH2 _ (Doc) 3_Gln_Trp_Ala_Val_P Ala-His_Leu_Leu_NH2 -(Doc)3-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle-NH2 -(Doc)3-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -(Doc)3-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -(Doc)3-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 - (Doc) 3-A印a-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu-NH: -(Doc)3-A印a-DPhe-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle-NH: -(000)3^印&-0 116-6111-11卬^1&,&1-617-附8-1^11-1^11^112 - (Doc) 3-DPhe-Gln-Trp-Ala-Val-e Ala-His-Leu-Leu_NH2 -(Doc)3-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -(Doc)3-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -(Doc)3-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -(Doc)3-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Doc-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Doc-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle_NH2 -Doc-A印a-Gln-Trp-Ala-Val- P Ala-His_Leu_Leu_NH2 -Doc-A印a-Gln-Trp-Ala-Val-e Ala_His_Leu_Nle_NH2 _Doc_A，_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2 -Doc-A印a-Gln-Trp-Ala-Val- P Ala_His-Phe-Nle_NH2 -Doc-A印a-Gln-Trp-Ala-Ala- P Ala_His-Phe-Nle_NH2 TABLE F [2002]<formula>formula see original document page 241</formula>
(Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc
Aepa--DPhe-Gln-Trp-Ala-Ala-PAla-His-Phe-NleDPhe--Gln--Trp-Ala-Val-PAla--His--Leu-Leu--NH2
DPhe--Gln--Trp-Ala-Val-PAla--His--Leu_Nle--NH2
DPhe--Gln--Trp-Ala-Val-Gly-His-Leu-Leu-NH2DAla--Gln--Trp-Ala-Val-PAla--His--Phe-Nle--NH2
DPhe--Gln--Trp-Ala-Ala-PAla--His--Phe-Nle--NH2
Aepa--Gln--Trp-Ala-Val-PAla--His--Phe-Nle--NH2
Aepa--Gln--Trp-Ala-Ala-PAla--His--Phe-Nle--NH2
-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -Gln-Trp-Ala-Val-P Ala-His-Leu-Nle_NH2 -Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Gln-Trp-Ala-Val-P Ala-His-Phe-Nle_NH2 -Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle_NH2
_Aepa_ (Doc) 4-_Aepa_ (Doc) 4-_Aepa_ (Doc) 4-_Aepa_ (Doc) 4-_Aepa_ (Doc) 4--(Doc) 4_Aepa_ -(Doc) 4_Aepa_ -(Doc) 4_Aepa_ -Aepa_ (Doc)2--Aepa_ (Doc)2--Aepa_ (Doc)2--Aepa_ (Doc)2--Aepa_ (Doc)2-
Gln--Trp--Ala--Val--Ala_His_Leu_Leu_NH2
Gln--Trp--Ala--Val-Ala-His-Leu-Nle-NH2
Gln--Trp--Ala--Val--Gly-His-Leu-Leu-NH2
Gln--Trp--Ala--Val-Ala-His-Phe-Nle-NH2
Gln--Trp--Ala--Ala-Ala-His-Phe-Nle-NH2
Gln--Trp--Ala--Val-Ala-His-Leu-Leu-NH2
Gln--Trp--Ala--Val-Ala-His-Leu-Nle-NH2
Gln--Trp--Ala--Val--Gly-His-Leu-Leu-NH2
-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala_His_Leu_Leu_NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2
-A印a-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2[2036] - (Doc) 2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 - (Doc) 2-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 - (Doc) 2-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 - (Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu-NH: - (Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH: -(00。)2^印&-0 116-6111-11卬^1&,&1-617-附8-1^11-1^11^112 - (Doc) 2-A印a-DAla-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH: - (Doc) 2-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH: -A印a- (Doc) 2-Gln-Trp-Ala_Val- P Ala-His-Ala-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -(Doc)2-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala_Val- P Ala-His-Ala-Nle-NH: -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 _ (Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Ala-Nle-NH2 -A印a- (Doc) 4-Gln-Trp-Ala_Val- P Ala-His-Ala-Nle-NH2 -(Doc)4-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 - (Doc) 4-G ln-Trp-Ala-Val-P Ala-His-Ala-Nle-NH2 -A印a- (Doc) 4-DPhe-Gln-Trp-Ala_Val- P Ala-His-Ala-Nle-NH: - (Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH: _ (Doc) 4-DPhe-Gln-Trp-Ala-Val-P Ala-His-Ala-Nle-NH2 - (Doc) 2-A印a-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH2 - (Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH: -A印a- (Doc) 3-Gln-Trp-Ala_Val- P Ala—His-Leu-Leu_NH2 -A印a- (Doc) 3-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle_NH2 -A印a- (Doc) 3-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -A印a-(Doc)3-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH2 -A印a- (Doc) 3-Gln-Trp-Ala_Ala- P Ala-His-Phe-Nle_NH2 -A印a-Doc-Gln-Trp-Ala-Val- P Ala-His_Leu_Leu_NH2 -A印a-Doc-Gln-Trp-Ala-Val- P Ala_His-Leu_Nle_NH2 4印&-00(3-6111-11"^1&,&1-617-附8-1^11-1^11^112 -A印a-Doc-Gln-Trp-Ala-Val- P Ala_His-Phe-Nle_NH2 -A印a-Doc-Gln-Trp-Ala-Ala- P Ala_His-Phe-Nle_NH2 - (Doc) 3-Gln-Trp-Ala-Val- P Ala—His-Leu-Leu_NH2 - (Doc) 3-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 - (Doc) 3-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -(Doc)3-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 - (Doc) 3-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 - (Doc) 3-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu-NH: - (Doc) 3-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH:[2075] - (Doc) 3-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH: - (Doc) 3-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 - (Doc) 3-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 - (Doc) 3-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -(Doc)3—DAla-Gln-Trp-Ala—Val-P Ala-His-Phe—Nle_NH2 -(Doc)3-DPhe-Gin—Trp—Ala—Ala—P Ala—His—Phe—Nle—NH2 -Doc-Gin-Trp-Ala-Val-0 Ala-His-Leu-Leu-NH2 -Doc-Gln-Trp-Ala-Val-0 Ala-His-Leu-Nle-NH2 -Doc-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Doc-Gln-Trp-Ala-Val-3 Ala-His-Phe-Nle-NH2 —Doc—Gin—Trp-Ala-Ala-3 Ala-His-Phe-Nle—NH2 -Doc-A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu-NH2 -Doc-A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2 -Doc-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Doc-A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -Doc-A印a-Gln-Trp-Ala-Ala- P Ala_His-Phe-Nle_NH2 [2091] <formula>formula see original document page 243</formula><formula>formula see original document page 244</formula>-A^a-(Doc)3—N
pGlu-His-Trp-Ser-Tyr —g^pLeu-Arg-Pro-Gly-NH2 -A印a-(Doc)4一N扁
H
pGlu-His-Trp-Ser-Tyr — N^YLeu-Arg-Pro-Gly-NH2
-Aepa —N-H
/>rLeu-Arg-Pro-Gly-NH2 pGlu-His-Trp-Ser-Tyr —N & a J 2
H
-Aepa-(Doc)2—N H
pGlu-His-Trp-Ser-Tyr —N^YLeu-Arg-Pro-Gly-NH2
-Aepa — N-H
pGlu-His-Trp-Ser-Tyr — N^pLeu-Arg-Pro-NHEt
H
O
-Aepa-(Doc)2—N-H
pGlu-His-Trp-Ser-Tyr—N"^YLeu-Arg國Pro-NHEt
-Aepa-(Doc)4 — N-H
pGlu-His-Trp-Ser-His—N、Trp-Tyr-Pro-Gly-NH2<formula>formula see original document page 246</formula><formula>formula see original document page 0</formula><formula>formula see original document page 248</formula><formula>formula see original document page 249</formula>-Aepa-(Doc)4 —n
pGlu-His-Trp-Ser-Tyr — j^^y Leu-Arg-Pro-Gly-NH2
H O
rx H
-Doc — N
pGlu-His-Trp-Ser誦Ty卜j^^Leu-Arg-Pro-G^NH2
H
-(Doc)2 —n
pGlu-His-Trp-Ser-Tyr — N"^Leu-Arg-Pr0-Gly-NH2 H
-(Doc)3—N
pGlu-His-Trp-Ser-Tyr —1st
H
-(Doc)4 —N
-Leu-Arg-Pro-Gly-NH2
O
pGlu-His-Trp-Ser-Tyr — N^YLeu-Arg-Pro-Gly-NH2
H
o -A印a- (Doc) 4-DPhe-Gln-Trp-Ala_Val- P Ala-His-Leu-Leu_NH2 -A印a-(Doc)4-DPhe-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle_NH2 4印&-(00。)4-0 116-6111-11卬^1&,&1-617-附8-1^11-1^11^112 —A印a-(Doc)4-DAla-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH2 -A印a-(Doc)4-DPhe-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle_NH2 - (Doc) 4-A印a-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc)4-A印a-DPhe-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle_NH2 -(00。)4^印&-0 116-6111-11卬^1&,&1-617-附8-1^11-1^11^112 -(Doc)4-A印a-DAla-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH2 -(Doc)HSDGIFTDSYSRYRKQMAVKKYLAAVL(P Ala)KRYKQRVKNK_NH2 - (Doc)HSDGIFTDSYSRYRKQMAVKKYLAAVL(Ava)KRYKQRVKNK_NH2 - (Doc) HSDGIFTDSYSRYRKQMAVKKYLAAVLGKRYKQR (A6c) KNK_NH2 - (Doc) HSDGIFTDSYSRYRKQMA (A5c) KKYLAAVLGKRYKQRVKNK_NH2 - (A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVL ( P Ala) KRYKQRVKNK_NH2<formula>formula see original document page 251</formula>pGlu-His-Trp-Ser-Tyr—g^pLeu-Arg-Pro-Gly-NHs
252
-Doc—n-H
pGlu-His-Trp-Ser-Tyr—M""^Leu-Arg-Pro-Gly-NH2 -(Doc)21
pGlu-His-Trp-Ser-Tyr—j^^^Leu—Arg—Pro_G|y_NH2
-(Doc)3 —N hi
pGlu-His-Trp-Ser-Tyr —S^^Leu-Arg-Pro-Gly-NH2
-(Doc)4 —n-H
pGlu-His-Trp-Ser-Tyr —N/\^Leu_Arg_Pr0-G|y_NH2
-Doc —n-H
pGlu-His-Trp-Ser-Tyr—N^^Leu-Arg-Pro-Gly-Nh^
H f
-(Doc)2_[j
pGlu-His-Trp-Ser-Tyr—N^Y"Leu-Arg-Pr0—G|y-NH2
H
O
_(Doc)3-fj
-Leu-Arg-Pro-Gly-NH2
O
pGlu-His-Trp-Ser-Tyr --(Doc)4—N<formula>formula see original document page 253</formula><formula>formula see original document page 254</formula><formula>formula see original document page 255</formula><formula>formula see original document page 256</formula><formula>formula see original document page 257</formula>-(Doc)2-Aepa —n H
pGlu-His-Trp-Ser-His —m
H
Trp-Tyr-Pro-Gly-NH
-Aep3-(Doc)2—n H
pGlu-His-Trp-Ser-His — N
H
Trp-Tyr-Pro-Gly-NH: [2145] [2146] [2147] [2148] [2149] [2150] [2151] [2152] [2153] [2154] [2155] [2156] [2157] [2159] [2160] [2161] [2162] [2163] [2164] [2165] [2166] [2167]
-Doc-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 -(Doc) 2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 -(Doc) 3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 -(Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 -(Doc) 5-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 -(Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 _Doc_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2 _ (Doc) 2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH: _ (Doc) 3_Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH: _ (Doc) 5_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH: _ (Doc) 6_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH: _ (A印a) 2_DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Val—Cys) _Thr_NH2
_Aepa_Doc_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2 -A印a- (Doc) 2-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: -A印a- (Doc) 3-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: -A印a- (Doc) 4-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: _Doc_Aepa_DPhe_cyclo (Cys_3 ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _ (Doc) 2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH: _ (Doc) 3_Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH: _ (Doc) 5_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH: _ (Doc) 6_Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH: _ (A印a) 2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH2[2168] -Doc-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 - (Doc) 2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 - (Doc) 3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 - (Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 - (Doc) 5-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 - (Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 - (Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 - (Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 - (Doc) 4-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 -Doc-A印a-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 _ (Doc) 2-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 _ (Doc) 3-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 _ (Doc) 4-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 _ (Doc) s-A印a-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 _ (Doc) 6-A印a-Caeg-cydo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 _ (A印a) 2-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 -Doc-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 _ (Doc) 2-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 _ (Doc) 3-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 _ (Doc) 4-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 _ (Doc) 5-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 _ (Doc) 6-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 -Doc-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 _ (Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 - (Doc) 4-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 5-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 6-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 6-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 4-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -A印a-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 4-A印a-Lys-DTyr-DTyr-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) -Thr-NH: - (Doc) 4-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2[2207] [2208] [2209] [2210] [2211] [2212]
-Aepa-DPhe-cyclo(Cys_Tyr-DTrp-Lys-Abu-Cys)_Thr-NH2
-A印3-Lys-DTyr-DTyr_cyclo (Cys-Tyr-DTrp_Lys_Abu_Cys) -Thr_NH2
-A印3-DPhe-cyclo (Cys_Tyr_DTrp-Lys_Abu_Cys) _Thr_NH2
-(Doc) 2-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2
_ (Doc) 4-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH:
-(Doc)4-Aepa-G aba — N ~\-(Doc)4-Aepa-Gaba —N
pGlu-His-Trp-Ser-Tyr
-Aepa-(Doc)4-Gaba —n
pGlu-His-Trp-Ser-Tyr
H
-(Doc)4-Gaba—N
H O
Leu-Arg-Pro-Gly-NH:
、/^Y"Leu-Arg-Pro-Gly-NH2 H O
pGlu-His-Trp-Ser-Tyr、N Leu-Arg-Pro-Gly-NH2
H O _(Doc)6-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr_NH2 - (Doc) 4-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2 -A印a-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 4-A印a-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -(Doc)4-A印a-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr_NH2 DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) -Thr_NH2 -A印a-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 4-A印a-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr-NH2 -A印a-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DT卬-Lys-Abu-Cys) -Thr_NH2 -A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) -Thr-NH2 -A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) -Thr-NH2 -(Doc)2-A印a-DPhe-cyclo(Cys-3ITy卜DTrp-Lys-Val-Cys)_Thr_NH2 —(Doc)2-A印a-DPhe-cyclo(Cys-3ITy卜DTrp—Lys—Val—Cys)_Thr_NH2 _ (Doc) 2-A印a-Caeg-cycl。 (DCys-3Pal—DTrp-Lys—DCys) —Thr (Bzl) _Tyr_NH2 _ (Doc) 4-A印a-Caeg-cycl。 (DCys-3Pal-DTrp-Lys-DCys) -Thr (Bzl) _Tyr_NH2[2231 ] -A印a-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 4-A印a-Lys-DTyr-DTyr-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) -Thr-NH: -A印a-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 2-A印a-DPhe-cydo (Cys-3ITyr-DTrp-Lys-Val—Cys) _Thr_NH2 _ (Doc) 2-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 _ (Doc) 4-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 -Doc-A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 2-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -(00。)3^印3-0 116-。7。10(〇78-171-011卬-1^8^1311-〇78)-1111~^112 - (Doc) s-A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 6-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a) 2-DPhe_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -Doc-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 2-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 3-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 4-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 5-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 6-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 _Doc_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 - (Doc) 2-A印a-Lys-DTyr-DTyr-cydo (Cys-Tyr-DTrp-Lys-Abu-Cys) -Thr-NH: - (Doc) 3-A印a-Lys-DTyr-DTyr-cydo (Cys-Tyr-DTrp-Lys-Abu-Cys) -Thr-NH: _ (Doc) 4_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 5_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: - (Doc) 6-A印a-Lys-DTyr-DTyr-cydo (Cys-Tyr-DTrp-Lys-Abu-Cys) -Thr-NH: - (A印a) 2-Lys-DTyr-DTyr_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -Doc-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 2-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 3-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 4-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 5-Lys-DTy r-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 6-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 _Aep3_Doc_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Aepa_ (Doc) 2_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH: -A印a- (Doc) 3-Lys-DTyr-DTyr_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) -Thr-NH: -A印a- (Doc) 4-Lys-DTyr-DTyr_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) -Thr-NH: -A印a-Doc-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2[2270] -A印a- (Doc) 2-DPhe_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 ^印3-(00。)3-0 116-。7。10(〇78-171-011卬-1^8^1311-〇78)-1111~^112 -A印a- (Doc) 4-DPhe_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 _ (Doc) 6-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 _ (Doc) 4-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 -A印a-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 _ (Doc) 4-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 _ (Doc) 4-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 -A印a-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 Doc-A印a-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 _ (Doc) 2-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 _ (Doc) 3-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 _ (Doc) 4-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 _ (Doc) s-A印a-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 _ (Doc) 6-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 _ (A印a) 2_Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 [2288] Doc-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 _ (Doc) 2-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 _ (Doc) 3-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 _ (Doc) 4-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 _ (Doc) 5-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 _ (Doc) 6-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 -A印a-Doc-Caeg-cyclo (DCys-3 Pal-DTrp-Lys-DCys) -Thr (Bzl) _Tyr_NH2 —A印a— (Doc) 2_Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 -A印a- (Doc) 3_Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 -A印a- (Doc) 4_Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 -A印a-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 4-A印a-Lys-DTyr-DTyr-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) -Thr-NH: -A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 —(Doc)2-A印a-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr-NH2 _ (Doc) 2-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 -A印a- (Doc) 4-Gaba-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle_NH2 - (Doc) 4-A印a-Gaba-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle_NH2 - (Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 [2306]<formula>formula see original document page 264</formula>
-(Doc)HSDAVFTDNYTRLRKQ(Nle)AVKKYLNSILN_NH2
-(Doc)HSDAVFTDNYTRLRKQMAVKKYLNSILN-NH2
-(Doc)HSDAVFTDNYTRLRKQMAVKKALNSILN-NH2
-(Doc)HSDAVFTDNYTRLRKQMAVKKLLNSILN-NH2
-(A印a) HSDAVFTDNYTRLRKQ (Nle) AVKKYLNSILN_NH2
-(A印a) HSDAVFTDNYTRLRKQMAVKKYLNS ILN-NH2
-(A印a) HSDAVFTDNYTRLRKQMAVKKALNS ILN-NH2
-(A印a) HSDAVFTDNYTRLRKQMAVKKLLNS ILN-NH2
-A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala—His-Leu-Leu_NH2<formula>formula see original document page 265</formula>
-(Doc) 2-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2<formula>formula see original document page 265</formula>
-A印a- (Doc) 4-Gaba-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2 -(Doc) 4-A印a-Gaba-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle_NH2<formula>formula see original document page 266</formula><formula>formula see original document page 267</formula>[2349] -A印a- (Doc) 3-DPhe-Gln_Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 - (Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2 -(Doc)3-A印a-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle-NH2 - (Doc) 3-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 - (Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH2 - (Doc) 3-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 -A印a-Doc-DPhe-Gln-Trp-Ala-Val- P Ala_His-Leu_Leu_NH2 -A印a-Doc-DPhe-Gln-Trp-Ala-Val- P Ala_His-Leu_Nle_NH2 4印&-00(3-0 116-6111-11"^1&,&1-617-附8-1^11-1^11^112 -A印a-Doc-DAla-Gln-Trp-Ala-Val- P Ala_His-Phe-Nle_NH2 -A印a-Doc-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 -A印a- (Doc) 4_Gaba_Gln_Trp_Ala_Val_ P Ala_His_Leu_Leu_NH2 _(Doc)4_A，_Gaba_Gln_Trp_Ala_Val_e Ala_His_Leu_Leu_NH2 - (Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -A印a-(Doc)4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu-NH: - (Doc) 4-A印a-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu-NH: - (Doc) 4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2 -A印a- (Doc) 4-Gaba-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle_NH2 - (Doc) 4—A印a-Gaba-Gln-Trp-Ala-Va1— P Ala-His-Leu-Nle_NH2 - (Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -A印a-(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2 - (Doc) 4-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2 -(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH)-Leu_NH2 [2374]
-A印a.
(Doc) 2-Gln-Trp-Ala-Val-P Ala—His—Leu—Leu—NH:<formula>formula see original document page 269</formula>[2386][2387][2388][2389][2390][2391][2392]
-Sue-A印a-(Doc)3-Gaba-Gin-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-Sue-A印a- (Doc) 3-Gin-Trp-Ala-Val- e Ala-His-Leu-Nle-NH2-Sue- (Doc) fA印a-Gin-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2-Sue- (Doc) 3-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2-Suc-A印a- (Doc) 3-DPhe-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle_NH2-Sue- (Doc) 3-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle_NH2
Suc-Aepa-(Doc)
pGlu-His-Trp-Ser-Tyr zj^j 。Suc-Aepa-(Doc)5、NH
Leu-Arg-Pro-Gly-NH2
pGlu-His-Trp-Ser-Tyr—B &Suc-(Doc)3-Aepa 、fvjn
Leu-Arg-Pro-Gly-NH2
pGlu'
-His-Trp-Ser-Tyr-B & ' 2
Suc-(Doc)5-Aepa
pGlu-His-Trp-Ser-TyrZ[2j 凸
Leu-Arg-Pro-Gly-NH2
0<
。1 o ct 、0q v、!_i - oh
-A印a-(Doc)2-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu-NH2
270[2395] -A印a- (Doc) 2-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle_NH2 -A印a- (Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -A印a- (Doc) 2-Gln-Trp-Ala_Val- P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 2-Gln-Trp-Ala_Ala- P Ala-His-Phe-Nle_NH2 -A印a-Gln-Trp-Ala-Val- P Ala_His_Leu_Leu_NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2 -A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 - (Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 - (Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 - (Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 - (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 - (Doc) 2-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala_Val- P Ala-His-Leu-Leu_NH2 -A印a-(Doc)2-DPhe-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle_NH2 -A印a-(Doc)2-DPhe-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Val-e Ala-His_Leu_Leu_N H2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 - (A印a) 2_ (Doc) 2-DPhe-Gln-Trp-Ala_Val- P Ala-His-Leu-Leu-NH: _ (A印a) 2_ (Doc) 2-DPhe-Gln-Trp-Ala_Val- P Ala-His—Leu—Nle—NH: -A印a- (Doc) 4-DPhe-Gln-Trp-Ala_Val- P Ala-His-Leu-Leu_NH2 -A印a-(Doc)4-DPhe-Gln-Trp-Ala-Val-e Ala-His-Leu-Nle_NH2 4印&-(00(3)4-0 116-6111-11卬^1&,&1-617-附8-1^11-1^11^112 -A印a- (Doc) 4-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-(Doc)4-DPhe-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle_NH2 - (Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2 - (Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle_NH2 - (Doc) 4-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 - (Doc) 4-A印a-DAla-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle_NH2 - (Doc) 4-A印a-DPhe-Gln-Trprp-Ala-Ala- P Ala-His-Phe-Nle_NH2 - (Doc) 4-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 - (Doc) 4-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 - (Doc) 4-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 - (Doc) 4-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -(Doc)4-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 - (Doc) 4-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 4-Gln-Trp-Ala_Val- P Ala-His-Leu-Leu_NH2
271[2434] -A印a- (Doc) 4-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle-NH2 -A印a- (Doc) 4-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -A印a- (Doc) 4-Gln-Trp-Ala_Val- P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 4-Gln-Trp-Ala_Ala- P Ala-His-Phe-Nle-NH2 - (Doc) 4—A印a-Gln-Trp-Ala-Va1— P Ala—His-Leu-Leu_NH2 - (Doc) 4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle_NH2 - (Doc) 4-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc)4-A印a-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH2 - (Doc) 4-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 - (Doc) 4-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 - (Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 - (Doc) 4-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 - (Doc) 4-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 - (Doc) 4-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala_Val- P Ala-His-Leu-Leu_NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle_NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -A印a-(Doc)2-DAla-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala_Ala- P Ala-His-Phe-Nle_NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2 4印&-0 116-6111-11"^1&,&1-617-附8-1^11-1^11^112 -A印a-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 - (Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 - (Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 _(Doc)2-DPhe-Gln-Trp-Ala-Va l-Gly-His-Leu-Leu_NH2 -(Doc)2-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 - (Doc) 2-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 - (Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2 - (Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle_NH2 - (Doc) 2-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 - (Doc) 2-A印a-DAla-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle_NH2 - (Doc) 2-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 -A印a- (Doc) 2-Gln-Trp-Ala_Val- P Ala-His-Ala-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -(Doc)2-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a-(Doc)2-DPhe-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2
272[2473] _ (Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Ala-Nle-NH2 -A印a- (Doc) 4-Gln-Trp-Ala_Val- P Ala-His-Ala-Nle-NH2 - (Doc) 4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH2 -(Doc)4-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH: - (Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH: _ (Doc) 4-DPhe-Gln-Trp-Ala-Val-P Ala-His-Ala-Nle-NH2 - (Doc) 2-A印a-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH2 -(Doc)2-A印a-DPhe-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH: -A印a- (Doc) 3-Gln-Trp-Ala_Val- P Ala—His-Leu-Leu_NH2 -A印a- (Doc) 3-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle-NH2 -A印a- (Doc) 3-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -A印a- (Doc) 3-Gln-Trp-Ala_Val- P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 3-Gln-Trp-Ala_Ala- P Ala-His-Phe-Nle_NH2 -A印a-Doc-Gln-Trp-Ala-Val- P Ala_His-Leu_Leu_NH2 -A印a-Doc-Gln-Trp-Ala-Val- P Ala_His-Leu_Nle_NH2 4印&-00(3-6111-11"^1&,&1-617-附8-1^11-1^11^112 -A印a-Doc-Gln-Trp-Ala-Val- P Ala_His-Phe-Nle_NH2 -A印a-Doc-Gln-Trp-Ala-Ala- P Ala_His-Phe-Nle_NH2 - (Doc) 3-Gln-Trp-Ala-Val- P Ala—His-Leu-Leu_NH2 - (Doc) 3-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 - (Doc) 3-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 - (Doc) 3-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 - (Doc) 3-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 - (Doc) 3-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu-NH: - (Doc) 3-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH: - (Doc) 3-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 - (Doc) 3-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc)3-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 - (Doc) 3-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 - (Doc) 3-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 - (Doc) 3-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Doc-Gln-Trp-Ala-Val-Gly-His-Leu-Leu_NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Doc-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 [2510]
273<formula>formula see original document page 274</formula><formula>formula see original document page 275</formula><formula>formula see original document page 276</formula>H
-(Doc)2-Aepa 一N^
pGlu-His-Trp-Ser-Tyr 、N'
H
O
-Leu-Arg-Pro-Gly-NH2
H
pGlu-His-Trp-Ser-Tyr —n'
H
O
-Leu-Arg-Pro-Gly-NH2
-(Doc)4-Aepa —N
pGlu-His-Trp-Ser-Tyr.—n'
H
-Leu-Arg-Pro-Gly-NH2
O
H
-A印3-(Doc);2 — N
2 '、^>
、
pGlu-His-Trp-Ser-Tyr—N'
H
-Leu-Arg-Pro-Gly-NH2
O
-Aepa-(Doc)3 _N
pGlu-His-Trp-Ser-Tyr
y^VLeu-Arg-Pro-Gly-NH2 H O
H
-Aepa-(Doc)4 — N
pGlu-His-Trp-Ser-Tyr—N YLeu-Arg-Pra-Gly-NH2
H
-Doc —N
pGlu-His-Trp-Ser-Tyr 、N LeU-Arg-Pro-Gly-NH2
H O<formula>formula see original document page 278</formula>[2515] -HSDGIFTDSYSRYRKQMAVKKYLAAVL(P Ala)KRYKQRVKNK_NH2 -HSDGIFTDSYSRYRKQMAVKKYLAAVL(Ava)KRYKQRVKNK_NH2 -HSDGIFTDSYSRYRKQMAVKKYLAAVLGKRYKQR (A6c) KNK_NH2 -HSDGIFTDSYSRYRKQMA (A5c) KKYLAAVLGKRYKQRVKNK_NH2 - (A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVL ( P Ala) KRYKQRVKNK_NH2 - (A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVL (Ava) KRYKQRVKNK_NH2 - (A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVLGKRYKQR (A6c) KNK_NH2 - (A印a) HSDGIFTDSYSRYRKQMA (A5c) KKYLAAVLGKRYKQRVKNK_NH2 - (Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 - (Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val—Cys) _Thr_NH2 - (Doc) 4-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 -Doc-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 - (Doc) 2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 - (Doc) 3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val—Cys)_Thr_NH2 - (Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 - (Doc) 5-DPhe_cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 - (Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 -Doc-A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 - (Doc) 2-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: - (Doc) 3—A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Val—Cys) —Thr—NH:
278[2539] - (Doc) s-A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: - (Doc) 6-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: - (A印a) 2-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 -A印a-Doc-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 -A印a- (Doc) 2-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: -A印a- (Doc) 3-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: -A印a- (Doc) 4-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: -Doc-A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 - (Doc) 2-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Thr-Cys) -Thr-NH: - (Doc) 3—A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Thr—Cys) —Thr—NH: - (Doc) s-A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Thr-Cys) -Thr-NH: - (Doc) 6-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Thr-Cys) -Thr-NH: - (A印a) 2-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 -Doc-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 - (Doc) 2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 - (Doc) 3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 - (Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 - (Doc) 5-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr—Cys)_Thr_NH2 - (Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 - (Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr—Cys)_Thr_NH2 - (Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 - (Doc) 4—A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Thr—Cys) —Thr—NH: -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Thr-Cys)_Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Thr-Cys) _Thr_NH2 [2565]
279<formula>formula see original document page 280</formula><formula>formula see original document page 281</formula><formula>formula see original document page 282</formula>
<formula>formula see original document page 282</formula>
<formula>formula see original document page 282</formula><formula>formula see original document page 283</formula><formula>formula see original document page 284</formula> -A印a-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) -Thr-NH: -DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2 -A印a-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) -Thr-NH
pGlu-His-Trp-Ser-Tyr ^"fj & 。-(Doc)4-Aepa
PGiu-His-Trp-Ser-TyrYYLeu-Arg-pro-G|y-NH2
-(Doc).[2575] -A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 _ (Doc) 2-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH: _ (Doc) 4-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH: _Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -Doc-A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -(00。)2^印&-0 116-。7。10(〇78-31171-011"-1^8^1311-〇78)-1111~^112 - (Doc) 3-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) s-A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 6-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (A印a) 2-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -Doc-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 5-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 4-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 6-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 4-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 _Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 - (Doc) 4-A印a-Lys-DTyr-DTyr-cydo (Cys-Tyr-DTrp-Lys-Abu-Cys) -Thr-NH: - (Doc) 4-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2[2606] -A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 _Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 4_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 —(Doc)2-A印a-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)-Thr-NH2 _ (Doc) 2-A印a-Caeg-cydo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 _ (Doc) 4-A印a-Caeg-cydo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 -Doc-A印a-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -(00。)2^印3-0 116-。7。10(〇78-171-011卬-1^8^1311-〇78)-1111~^112 - (Doc) 3-A印a-DPhe-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -(00。)5^印3-0 116-。7。10(〇78-171-011卬-1^8^1311-〇78)-1111~^112 -(00。)6^印&-0 116-。7。10(〇78-171-011卬-1^8^1311-〇78)-1111~^112 - (A印a) 2-DPhe_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -Doc-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 2-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 3-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 4-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 5-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr_NH4 - (Doc) 6-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 _Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Doc_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 - (Doc) 2-A印a-Lys-DTyr-DTyr-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 3-A印a-Lys-DTyr-DTyr-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 _ (Doc) 4_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 - (Doc) s-A印a-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (Doc) 6-A印a-Lys-DTyr-DTyr-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 - (A印a) 2-Lys-DTyr-DTyr_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 _Doc_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 - (Doc) 2-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 3-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 4-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 5-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 - (Doc) 6-Lys-DTyr-DTyr-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys)_Thr_NH2 _Aep3_Doc_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -A印a- (Doc) 2-Lys-DTyr-DTyr_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a- (Doc) 3-Lys-DTyr-DTyr_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 _Aepa_ (Doc) 4_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2[2645] -A印a-Doc-DPhe-cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a- (Doc) 2-DPhe_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a- (Doc) 3-DPhe_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 -A印a- (Doc) 4-DPhe_cyclo (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 _ (Doc) 6-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 _ (Doc) 4-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 -Caeg-cyclo(DCys-3Pal-DTrp-Lys-DCys)-Thr(Bzl)_Tyr_NH2 -A印a-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 _ (Doc) 4-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 _ (Doc) 4-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 -Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 -A印a-Caeg-cyclc (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 -Doc-A印a-Caeg-cyclo (DCys-3Pal-DTrp-Lys-DCys) -Thr (Bzl) _Tyr_NH2 _ (Doc) 2-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 _ (Doc) 3-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 _ (Doc) 4-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 _ (Doc) s-A印a-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 _ (Doc) 6-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 _ (A印a) 2_Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 -Doc-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 _ (Doc) 2-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 _ (Doc) 3-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 _ (Doc) 4-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 _ (Doc) 5-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 _ (Doc) 6-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2 -A印a-Doc-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 -A印a- (Doc) 2_Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 -A印a- (Doc) 3_Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2 -A印a- (Doc) 4_Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2 -HSDAVFTDNYTRLRKQ(Nle)AVKKYLNSILN_NH2 -HSDAVFTDNYTRLRKQMAVKKYLNSILN_NH2 -HSDAVFTDNYTRLRKQMAVKKALNSILN_NH2 -HSDAVFTDNYTRLRKQMAVKKLLNSILN-NH2 - (A印a) HSDAVFTDNYTRLRKQ (Nle) AVKKYLNSILN_NH2 - (A印a) HSDAVFTDNYTRLRKQMAVKKYLNS I LN_NH2 - (A印a) HSDAVFTDNYTRLRKQMAVKKALNS I LN_NH2 - (A印a) HSDAVFTDNYTRLRKQMAVKKLLNSILN-NH2 _Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 - (Doc) 4-A印a-Lys-DTyr-DTyr-cycl。 (Cys-Tyr-DTrp-Lys-Abu-Cys) -Thr-NH:
287[2684] [2685] [2686]
-Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
-(Doc) 2-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 [2688] [2689] [2690] [2691] [2692] [2693] [2694] [2695] [2696] [2697] [2698] [2699] [2700] [2701] [2702] [2704] [2705] [2706] [2707]
(Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc (Doc
(Doc), (Doc), (Doc)( (Doc), (Doc),
-Aepa_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -DPhe-cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -DPhe-cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 -Aep3_Lys_DTyr_DTyr_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 -Lys_DTyr_DTyr_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 -Lys_DTyr_DTyr_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 -Aepa-Caeg-cyclo (DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2 -Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 -Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2
-Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -DPhe-cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -DPhe-cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2[2708] [2709] [2710] [2711] [2712] [2713] [2714] [2715] [2716] [2717] [2718]
NH2
_ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
_ (Doc) 4_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2
_ (Doc) 4_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2
_ (Doc) 6_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2
_ (Doc) 4_Aep3_Lys_DTyr_DTyr_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH:
_ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2
_ (Doc) 6_Lys_DTyr_DTyr_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2
_ (Doc) 4_Aepa_Caeg_cyclo(DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2
-(Doc) 4-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2
-(Doc) 6-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2
_Suc_ (Doc) 3_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
_Suc_ (Doc) 3_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2
_Suc_ (Doc) 5_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2
_Suc_ (Doc) 3_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
_Suc_ (Doc) 3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
_Suc_ (Doc) 5_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2
_Suc_ (Doc) 3_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2
_Suc_ (Doc) 3_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2
_Suc_ (Doc) 5_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH2
_Suc_ (Doc) 3_Aep3_Lys_DTyr_DTyr_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_
_Suc_ (Doc) 3_Lys_DTyr_DTyr_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _Suc_ (Doc) 5_Lys_DTyr_DTyr_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _Suc_ (Doc) 3_Aep3_Caeg_cyclo (DCys_3P3l_DTrp_Lys_DCys)_Thr(Bzl)_Tyr_NH2 _Suc_ (Doc) 3_Caeg_cyclo(DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2 _Suc_ (Doc) 5_Caeg_cyclo (DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2 _Suc_ (Doc) 4_Caeg_cyclo(DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2 _Suc_ (Doc) 5_Aep3_Caeg_cyclo(DCys_3P3l_DTrp_Lys_DCys)_Thr(Bzl)_Tyr_NH2 _Suc_ (Doc) 4_Aep3_Caeg_cyclo (DCys_3P3l_DTrp_Lys_DCys)_Thr(Bzl)_Tyr_NH2 生物学测试[2738] 生长抑素受体_放射性配体的结合实验 体外受体结合试验的细胞膜的制备在冰冷却的50mM Tris-HCl中，匀化 (Polytron setting 6， 15秒)表达人类生长抑素受体亚型(hSSTR-l， hSSTR-2， hSSTR-3， hSSTR-4，或hSSTR-5)的CH0-K1细胞，39， 000g(10分钟)下离心两次，再重新悬浮于新 鲜的缓冲液中。将得到的小球再悬浮于10mM Tris-HCl以备用于结合实验中。为进行 hSSTR-l，hSSTR-3和hSSTR-4的结合实验，将等份的细胞膜制备物与含BSA(0. 2% )和O. 05 nM[125I-Tyrll]SRIF-14的50薩EPES(pH7. 4) 、MgCl2(5mM) —起温育(90分钟/25。C )。进行 实验的最终体积为0. 3ml 。为进行hSSTR-2和hSSTR-5的结合试验，分别将[125I] - [4- (2-羟 乙基)]-1-哌嗪乙酰基-DPhe-环(Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 (0. 05 nM)和 [^1]-DPhe-环(Cys-Tyr-DTrp-Lys-Val-Cys)-Thr-NH2作为放射性配体，温育时间为90分 钟/25。C。利用Brandel filtration manifold通过GF/C滤器快速过滤(预先浸在0. 3% 聚氮丙啶硫化物中)终止温育。然后用等份的5ml冰冷却的缓冲液清洗各管和滤器，各清 洗三次。特异性结合被定义为全部放射性配体结合物减去存在有lOOOnM SRIF-14(用于 hSSTR-l， hSSTR-3， hSSTR-4或hSSTR-5的受体结合试验)的结合物的差值或减去存在有1 OOOnMDPhe-c (Cys-Tyr-DTrp-Lys-Abu-Cys) _Thr_NH2 (用于hSSTR-2受体结合实验)的结合 物的差值。 体外生长实验 将培养的CHO-K1细胞或表达hSSTR-2受体的CHO-K1细胞接种于塑料24孔培养 板中，培养板中含10%牛胎血清(FBS)的RPMI1640培养基(DMEM)，接种密度为约104个 细胞/孔/1.0ml，进行体外增殖试验。将测试用的肽以所需浓度加入其中，培养(5%C02， 37t:，潮湿空气)1-3天。用无血清的RPMI基质洗涤细胞，使细胞胰蛋白酶化，再次悬浮于 RPMI1640(+10% FBS)中，用Coulter计数器，在1 : 20的稀释度下计细胞数。 [2742] LHRH放射性配体的结合 用于放射性配体结合研究的细胞膜的制备如下在20ml冰冷却的50mMTriS_HCl 中，用Brinkman Polytron(Westbury， NY ;setting 6， 15秒)匀化表达大鼠重组LHRH受体 的CHO-K1细胞。通过离心(39， 000g/10分钟)，洗涤匀化物两次，得到的小球再次悬浮于含 5mM MgCl^PO. 1XBSA(牛血清白蛋白)的50mM Tris-HCl中。将等份(0. 4ml)细胞膜制备 物与其中含有或不含有0.05ml未标记的竞争性测试肽的O. 05 nM[125I]D-Trp6 LHRH(2200 Ci/mmol) —起温育，进行结合测试实验。温育60分钟(4°C )后，，通过预先浸入0. 5 %聚 乙烯亚胺/0. 1% BSA中的GF/B过滤器(Brandel， Gaithersburg， MD)进行快速过滤，将结 合物[125I]D-Trp6LHRH与游离物分离开。然后用等份的5ml冰冷却的50mMTris-HCl清洗 过滤器三次，利用Y光谱(Wallac LKB， Gaithersburg, MD)计算捕获在过滤器上的结合物 的放射性。特异性结合被定义为全部[mi]D-Trp6LHRH结合物减去存在有lOOOnM D_Trp6 LHRH(Bachem， Torrence， CA)的结合物之差值。 [2744] 铃蟾肽/GRP放射性配体的结合 用于放射性配体结合研究的细胞膜的制备如下在20ml冰冷却的50mMTriS_HCl 中，用Brinkman Polytron(Westbury， NY ;setting 6， 15秒)匀化表达天然铃蟾肽/GRP受 体的AR42J大鼠胰腺细胞。通过离心(39,000 g/10分钟)，洗涤匀化物两次，得到的小球再 次悬浮于含2. 5 mM MgCl2和0. 1 % BSA的50mMTris_HCl中。将等份(0. 4ml)细胞膜制备物
290与其中含有或不含有0. 05ml未标记的竞争性测试肽的0. 05nM[125I-Tyr4]铃蟾肽(2200Ci/ mmol，New EnglandNuclear， Boston,MA) —起温育，进行结合测试实验。温育30分钟(4°C ) 后，通过预先浸入O. 3X聚乙烯亚胺中的GF/B过滤器(Brandel，Gaithersburg，MD)来进行 快速过滤，将结合物[125I_Tyr4]铃蟾肽与游离物分离开。然后用等份的5ml冰冷却的50mM Tris-HCl清洗过滤器三次，利用y光谱(Wallac LKB，Gaithersburg，MD)计算捕获在过滤 器上的结合物的放射性。特异性结合被定义为全部[125I_Tyr4]铃蟾肽结合物减去存在有 1000 nM铃蟾肽(Bachem， Torrence， CA)的结合物之差值。 本发明的一些化合物至少有一个不对称中心。根据分子的不同取代基可能还存在 其它不对称中心。每个不对称中心将产生两个光学异构体，所有光学异构体，无论是分离后 的、纯化的或部分纯化的光学异构体、外消旋混合物或非对应异构体混合物，都包括在本发 明范围之内。 本发明的化合物通常是以药学上可接受的酸加成盐形式提供，如由无机酸和有机 酸得到的盐。这些酸得实例包括盐酸、硝酸、硫酸、磷酸、甲酸、乙酸、三氟乙酸、丙酸、马来 酸、琥珀酸、D-酒石酸、L-酒石酸、丙二酸、甲磺酸等。此外，含有酸官能团如羧基的化合物， 可以以它们的无机盐形式分离出，其中反离子可以选自钠、钾、锂、钙、镁等，以及有机碱。 [2748] 药学上可接受的盐可以如此形成，将约1当量的本发明的化合物与约1当量或更 多的预期盐的适宜的相应酸相接触。制备盐的操作和盐的分离是本领域普通技术人员所公 知的方法。 本发明的化合物的给药形式可以是口服、胃肠外给药(如，肌内、腹膜内、静脉内
或皮下的注射或灌输)、鼻腔内、阴道内、直肠内、舌下或局部(topical)途径给药，也可与
药学上可接受的载体一同制成适于各种给药途径的剂型。因此，本发明描述了药物组合物，
其包括作为活性成分的至少一种本发明的化合物以及药学上可接受的载体。 口服固体剂型包括胶囊、片剂、丸剂、粉剂和颗粒剂。这些固体剂型中，活性化合物
与至少一种惰性的药学上可接受的载体混合，这些载体为如蔗糖、乳糖或淀粉。这些剂型还
可包括，如常规操作所包括的惰性稀释剂之外还包括其它物质，如诸如硬脂酸镁的润滑剂。
在胶囊、片剂和丸剂的剂型中还可包括缓冲剂。片剂和丸剂还可用肠溶衣制备。 口服液体剂型包括药学上可接受的乳剂、溶液、悬浮剂、糖浆、酊剂，这些剂型含有
本领域常用的惰性稀释剂，如水。除惰性稀释剂以外，组合物还可包括辅料，如润湿剂、乳化
剂和悬浮剂、甜味剂、轿味剂和芳香剂。 本发明的胃肠外给药的制剂包括无菌的水性或非水溶液、悬浮液或乳液。非水溶 剂或载体的实例为丙二醇、聚乙二醇、植物油，如橄榄油和玉米油、凝胶和可注射的有机酯，
如油酸乙酉旨。这些剂型还可包括辅料，如防腐齐U、润湿齐iJ、乳化剂和分散齐iJ。它们可通过利用
过滤器滤除细菌、将无菌物质加入组合物中、照射组合物或加热组合物的方法实现无菌化。 它们还可以制成无菌固体组合物，这样的无菌固体组合物可以在使用前溶于无菌水或其它 无菌可注射溶煤中。 直肠或阴道内给药的组合物优选为栓剂，其可包括，除活性物质以外的赋形剂，如 可可油或栓剂蜡。 鼻内或舌下给药的组合物可与本领域的常规赋形剂一同制备。 通常，本发明组合物中的有效量的活性成分是可变的，但活性成分的量与适宜的剂型相对应。所选择的剂量依据需要的治疗效果，依据给药途径，依据治疗时间而定，所有 这些因素都是本领域普通技术人员能够驾驭的。通常，施用于人类和其它动物，如哺乳动物 的剂量水平为每日0. 0001-100mg/kg体重。 优选的剂量范围是O. 01-10. 0mg/kg体重。这样的剂量可以每日单次给药，或分多 次给药。 其它实施方式 不背离本发明的范围和精神下，本发明的上述方法和体系的各种变化和调整都是 本领域技术人员显而易见的。尽管结合了具体实施例对本发明进行了描述，可以理解，本发 明不应该仅限于这些具体实施例。实施本发明时对所描述方式进行的对于医学、免疫学、药 理学、内分泌学或相关领域的技术人员而言是显而易见的各种改变都在本发明的保护范围 内。 说明书中所引的公布申请都全文引用于此。
权利要求
式(I)的化合物或其药学上可接受的盐X-B1-B2-B3-B4-Z(I)其中X是细胞毒物质或细胞抑制剂；B1，B2，B3和B4各自独立地是(Doc)m，(Aepa)n，-(C(O)-A1-A2-A3-A4-A5-C(O))s-或(氨基酸)p，A1和A5各自独立地是CR1R2；R1和R2各自独立地是H，F，Br，Cl，I，C(1-30)烷基，C(2-30)烯基，取代的C(1-30)烷基，取代的C(2-30)烯基，SR3，S(O)R4或S(O)2R5，或R1和R2共同形成C(3-30)环烷基，C(3-30)杂环基或C(5-30)芳环；R3，R4和R5各自独立地是C(1-30)烷基，C(2-30)烯基，取代的C(1-30)烷基，取代的C(2-30)烯基；A2，A3和A4各自独立地是CR6R7，O，S，(CH2)t或缺省；R6和R7各自独立地是H，F，Br，Cl，I，C(1-30)烷基，C(2-30)烯基，取代的C(1-30)烷基，取代的C(2-30)烯基，SR3，S(O)R4或S(O)2R5；或R6和R7共同形成环系；m独立地是0，1，2，3，4，5，6，7，8，9或10；n独立地是0，1，2，3，4，5，6，7，8，9或10；p独立地是0，1或2；s独立地是1，2，3，4或5；t各自独立地是0，1，2或3；Z是生物受体的配体、其类似物或所述配体或所述类似物的衍生物；条件是当X是多柔比星或多柔比星衍生物时，至少m和n之一不为0；且当X是紫杉醇或紫杉醇衍生物时，B1是(氨基酸)p，其中p为1或2。
2. 根据权利要求1所述的化合物，其中，X是细胞毒部分，或其药学上可接受的盐。
3. 根据权利要求2所述的化合物，其中X是蒽环霉素或其药学上可接受的盐。
4. 根据权利要求3所述的化合物，其中X是多柔比星或多柔比星衍生物或它们的药学 上可接受的盐。
5. 根据权利要求2所述的化合物，其中X是喜树碱、喜树碱衍生物、紫杉醇或紫杉醇衍 生物。
6. 根据权利要求5所述的化合物，其中所述的喜树碱衍生物为<image>image see original document page 3</image>
7.<image>image see original document page 2</image>接受的盐，其中所述紫杉醇衍生物为A.
8.根据权利要求4所述的化合物，其中X是多柔比星或多柔比星衍生物，或它们的药学上可接受的盐，其中所述多柔比星衍生物为
9. 根据权利要求l-8任意一项所述的化合物，其中，Z是生长抑素、铃蟾肽或LHRH或它 们的类似物，或所述配体的衍生物或衍生物的类似物，或它们的药学上可接受的盐。
10. 根据权利要求9所述的化合物，其中Z是下式的生长抑素类似物 _DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 ; -DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 ; _DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2 ; _DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 ; _Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2 ; _Caeg_cyclo (DCys_Pal_DTrp_Lys_DCys)_Thr(Bzl)_Tyr_NH2 ; -D2Nal-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]_Thr_NH2 ; -DPhe-cyclo[Cys_Phe_DTrp_Lys_Thr_Cys]-Thr-ol ^-cyclo ({4-(-NH-C2H4-NH-C0-0)Pro}-Phg-DTrp-Lys-Tyr(4_Bzl) -Phe);或 -DPhe-cyclo[Cys-Tyr-DTrp-Lys-Val-Cys]-Trp-NH2 ;或它们的药学上可接受的盐。
11. 根据权利要求9所述的化合物，其中，Z是下式的LHRH类似物Glp--His--Trp--Ser--Tyr--DLys (-)_Leu--Arg--Pro--Gly-NH2 ;Glp--His--Trp--Ser--Tyr--DOrn (-)_Leu--Arg--Pro--Gly-NH2 ;Glp--His--Trp--Ser--Tyr--DDab (-)_Leu--Arg--Pro--Gly-NH2 ;Glp--His--Trp--Ser--Tyr--DDap (-)_Leu--Arg--Pro--Gly-NH2 ;Glp--His--Trp--Ser--Tyr--DApa (-)_Leu--Arg--Pro--Gly-NH2 ;Glp--His--Trp--Ser--Tyr--DLys (_)_Leu--Arg--Pro--NHEt ;Glp--His--Trp--Ser--Tyr--DOrn (-)_Leu--Arg--Pro--NHEt ;Glp--His--Trp--Ser--Tyr--DDab (-)_Leu--Arg--Pro--NHEt ;Glp--His--Trp--Ser--Tyr--DDap (-)_Leu--Arg--Pro--NHEt ;Glp--His--Trp--Ser--His--DLys (_)_Trp-—Tyr--Pro--Gly-NH2 ;Glp_His_Trp_Ser_His_DOrn(_)_Trp_Tyr_Pro_Gly_NH2 ; Glp-His-Trp-Ser-His-DDab(-)-Trp-Tyr-Pro_Gly-NH2 ;或Glp-His-Trp-ser-His-DD即(-)-Trp-Tyr-Pro_Gly-NH2 ;或它们的药学上可接受的盐
12.根据权利要求9所述的化合物，其中，Z是下式的铃蟾肽类似物-Gln--Trp--Ala--Ala--P Ala-His-Phe-Nle-NH2 ;-Gln--Trp--Ala--Val--Gly-His-Leu-W (CH2_NH)-Gln--Trp--Ala--Val--Gly-His-Leu-W (CH2_NH)-Gln--Trp--Ala--Val--P Ala-His-Leu-Leu-NH2 ;-Gln--Trp--Ala--Val--P Ala-His-Leu-Nle-NH2 ;-Gln--Trp--Ala--Val--P Ala-Hls-Phe-Nle-NH2 ;-Gln--Trp--Ala--Val-Ala-His-Ala-Nle-NH2 ;-Gln--Trp--Ala--Val--P Ala-Ala-Phe-Nle-NH2 ;-Gln--Trp--Ala--Val--Gly-His-Leu-Leu-NH2 ;-Gln--Trp--Ala--Val--Gly-His-Leu-Met-NH2 ;-Gln--Trp--Ala--Val--Gly-His-Phe-Met-NH2 ;-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 ; -DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 ; -DPhe-Gln-Trp-Ala-Val-P Ala-Ala-Phe-Nle-NH2 ; -DPhe-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 ; -DPhe-Gln-Trp-Ala-Val-P Ala-His-Ala-Nle-NH2 ; -DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu-NH2 ; -DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 ; -DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2_NH)-Leu_NH2 ; -DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2_NH)-Phe_NH2 ; -DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Met-NH2 ; -DPhe-Gln-Trp-Ala-Val-Gly-His-Phe-Met-NH2 ;-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 ;或它们的药学上可接受的盐。
13. 根据权利要求1所述的化合物，其中，至少m和n之一不为零；或这些化合物的药 物学上可接受的盐。
14. 根据权利要求1所述的化合物，其中，所述化合物包括下列结构的化合物或它们的 药学上可接受的盐<formula>formula see original document page 6</formula><formula>formula see original document page 7</formula><formula>formula see original document page 8</formula><formula>formula see original document page 9</formula><formula>formula see original document page 10</formula><formula>formula see original document page 11</formula><formula>formula see original document page 12</formula><formula>formula see original document page 13</formula><formula>formula see original document page 14</formula><formula>formula see original document page 15</formula>(Doc)4-Aepa-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-CysKThr-NH2Y^>^"Y* (Doc)4-Aepa-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-N H2wX/v^(Doc)4-Aepa-DPhe"Cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2(Doc)4-Lys-DTyr-DTyr-cydo(Cys-Tyr-DTrp-Lys-AbiJ-Cys)-Thr-NH::
15.根据权利要求13所述的化合物，其中，包括以下结构的化合物或其药学上可接受的盐<formula>formula see original document page 15</formula>或jj-Suc-(Doc)3-Ae;)a-DPMe"Cyclo(Cys-Ty&DTrp-Lys-A^-Cys)-THr-NH2(Doc)4-Gaba-Gln-Trp-Ala-Val-&Ala-His-Leu-Nie-NH7o m- v Y.(Doc)4-A印a-Gaba-Gln-Trp-A.a-Val-。Aia-His-Le'j-Ni^NH，(Doc)4-A印a-Gaba-Gin-Trp"Ala-Vai曙PAIa-His-Leu-Nle-NH,
16.根据权利要求14所述的化合物，其中，所述化合物包括以下化合物或它们的药学上可接受的盐(Doc)rLys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2([)oc)4-A印a-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH，(Doc)4-A印a-DPhe-cydo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH
17.根据权利要求16所述的化合物，其中，所述化合物包括下式化合物或其药学上可 接受的盐
18.根据权利要求16所述的化合物，其中，所述化合物包括下式化合物或其药学上可接受的盐
19.根据权利要求16所述的化合物，其中，所述化合物包括下式化合物或其药学上可接受的盐
20.可作为化学合成的中间体的化合物，其中，所述中间体包括下式化合物或它们的有机或无机盐H-Lys (Boc)-DTyr (tBu)-DTyr(tBu)-Cys(Trt)-Tyr(tBu)-DTrp(Boc)-Lys(Boc)-Abu-C ys (Trt) _Thr (tBu)-Rink Amide MBHA Resin;H-Doc-Doc-Doc-Doc-Lys(Boc)-DTyr(tBu)-DTyr (tBu)-Cys(Trt)-Tyr (tBu)-DTrp (Boc )_Lys(Boc)_Abu_Cys(Trt)_Thr(tBu)-Rink Amide MBHA Resin;H-Doc-Doc-Doc-Doc-Doc-Doc-Lys(Boc)-DTyr(tBu)-DTyr(tBu)-Cys(Trt)-Tyr(tBu)-DTrp(Boc)-Lys(Boc)-Abu-Cys(Trt)-Thr(tBu)-Rink Amide MBHA Resin;H-A印a-Lys (Boc) -DTyr (tBu) -DTyr (tBu) -Cys (Trt) -Tyr (tBu) -DTrp (Boc) -Lys (Boc)-Abu—Cys(Trt)_Thr(tBu)—Rink Amide MBHA Resin;(Doc)4-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH.(Doc)4-Aepa-DPhe-cyclo(Cy,s-Tyr-DTrp-Lys-Abu-Cys)-Thi、NH:(Doc)4-Aepa-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH<formula>formula see original document page 18</formula><formula>formula see original document page 19</formula> H—Aepa-(DoC)．-Gin(Trt)-Trp(BeC)-A1a—Val—p A1a—Hi S(Trt)-Leu—Leu—RinkAmideMgHA Resin；H—Aepa-(Dec)．-DPho—Gin(Trt)-Trp(goc)-Ala—Val—p Ala—Hi S(Trt)-Leu—Leu—RinkAmide MBHA ResinpGlu—Hi S(Trt)-Trp(goc)-Set(tgu)-Tyr(tgu)-DLys[N‘-Aepa]-Leu—Arg(Pbf)-Pro—Gly—Rink Amide MBHA Resin；pGlu—Hi S(Trt)-Trp(goc)-Set(tgu)-Tyr(tgu)-DLys[N‘-(Aepa-(Dec)4-)]-Leu—Arg(Pbf)-Pro—Gly—Rink Amide MBHA Resin；H-(Dec)．-Aepa—Caeg—DCys(Trt)-3Pal—DTrp(goc)-Lys(goc)-DCys(Trt)-Thr(gz 1)-Tyr(tgu)-Rink Amide MBHA Resin；H-(Dec)．-Aepa—DPhe—Cys(Trt)-3 ITyr—DTrp(goc)-Lys(goc)-Val—Cys(Trt)-Thr(tgu)-Rink Amide MBHA Resin<formula>formula see original document page 19</formula>H-DPhe-Cys(Trt)-Tyr(tBu)-DTrp(Boc)-Lys(Aloe)-Abu-Cys(Trt)-Thr(tBu)-Rink-A mide_MBHA_Resin ;Fmoc_Aepa_DPhe_Cys(Trt)_Tyr(tBu)_DTrp(Boc)_Lys(Aloe)_Abu_Cys (Trt)_Th r(tBu)_Rink_Amide_MBHA_Resin ;H-Doc-Doc-Doc-Doc-A印a-DPhe-Cys (Trt) -Tyr (tBu) -DTrp (Boc) -Lys (Aloe) -Abu-Cys (Trt)-Thr(tBu)-Rink-Amide-MBHA-Resin ; ;orH_Doc_Doc_Doc_Aepa_DPhe_Cys(Trt)_Tyr(tBu)-DTrp(Boc)_Lys(Aloe) _A bu-Cys (Trt)-Thr (tBu)_Rink_Amide_MBHA_Resin。
21.根据权利要求1所述的化合物，其中，所述化合物包括下式化合物 <formula>formula see original document page 20</formula>-A印a- (Doc) 4-Gaba-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH: _ (Doc) 4-A印a-Gaba-Gln-Trp-Ala-Va1- P Ala_His-Leu_Nle_NH:<formula>formula see original document page 21</formula>-A印a- (Doc) 3-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a- (Doc) 3-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 3-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -(Doc) 3-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -(Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH2 -(Doc) 3-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH2 -(Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2 -A印a-Doc-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 -A印a-Doc-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-A印a-Doc-DPhe-Gln-Trp-Ala-Val- P Ala_His_Leu_Nle_NH2-A印a-Doc-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2-Doc-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2-Doc-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-N le_NH2-Doc-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-Doc-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-Doc-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-(Doc)2-Gln-Trp-Ala-Ala-PAla-His-Phe-Nle-NH2-(Doc)2-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2-(Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2-(Doc) 4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-(Doc) 4-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-A印a-(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-(Doc) 4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-(Doc) 4-A印a-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-A印a-(Doc)4-Gaba-Gln-Trp-A la-Val-Gly-His-Leu-W (CH2NH) -Leu-NH:-(Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2_ (Doc) 4_Aepa_Gaba_Gln_Trp_Ala_Val_ P Ala_His_Leu_Leu_NH2-A印a- (Doc) 4-Gaba-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2-(Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2_ (Doc) 4-A印a-Gaba-Gln-Trp-Ala-Va1- P Ala_His-Leu_Nle_NH2-A印a- (Doc) 4-Gaba-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2-(Doc)2-Gln-Trp-Ala-Ala-PAla-His-Phe-Nle-NH2-(Doc)2-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2-(Doc) 2-Gln-Trp-Ala-Va 1-Gly-His-Leu-Leu-NH2-(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-(Doc) -(Doc) -(Doc) -A印a--A印a--A印a--A印a--A印a--(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -A印a' -A印a' -A印a' -A印a' -A印a' -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc4_Aepa-4_Aepa-4_Aepa-(Doc)4-(Doc), (Doc), (Doc). (Doc). 4-DPhe-4-DAla-4-DPhe-4-DPhe-4-DPhe-4_Aepa-4_Aepa-4_Aepa-4_Aepa-4_Aepa-(Doc). (Doc). (Doc). (Doc). (Doc).DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala_His_Leu_Leu_NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 2-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH: -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu-NH: -(Doc) 2-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -(Doc)2-DAla-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 _ (Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -A印a-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a- (Doc)4-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a- (Doc)4-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH: -(Doc)2-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -A印a- (Doc)2-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH: -(Doc)2-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 _ (Doc) 4-DPhe-Gln-Trp-Ala-Val-P Ala-His-Ala-Nle-N H2 -(Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH: -A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH: -(Doc)4-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -(Doc)4-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a- (Doc)2-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -(Doc)2-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH: -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -(Doc)2-DPhe-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -A印a- (Doc)4-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc)4-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc)4-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH: -(Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH: -(Doc)4-DPhe-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -(Doc)2-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH: -A印a- (Doc) 3-Gln-Trp-Ala-Val- P Ala—His-Leu-Leu_NH2-A印a- (Doc) 3-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2-A印a- (Doc) 3-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-A印a- (Doc) 3-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-A印a- (Doc) 3-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2-A印a-Doc-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2-A印a-Doc-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2_Aepa_Doc_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2-A印a-Doc-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-A印a-Doc-Gln-Trp-Ala-Ala- P Ala_His-Phe-Nle_NH2-(Doc) 3-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-(Doc) 3-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-(Doc) 3-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-(Doc)3-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2-(Doc)3-Gln-Trp-Ala-Ala-PAla-His-Phe-Nle-NH2-(Doc) 3-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2-(Doc)3-DAla-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2-(Doc) 3-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-(Doc) 3-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2_ (Doc) 3-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-(Doc) 3-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2-(Doc) 3-A印a-DAla-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH2-(Doc) 3-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-(Doc) 3-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH2-(Doc) 3-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2-Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-Doc-A印a-Gln-Trp-Ala-Ala- P Ala_His-Phe-Nle_NH2-Doc-A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2_Doc_Aepa_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2-Doc-A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2-Doc-A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2-Doc-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2-Doc-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2-Doc-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2_ (Doc) 4_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:<formula>formula see original document page 26</formula><formula>formula see original document page 27</formula><formula>formula see original document page 28</formula><formula>formula see original document page 29</formula>(Doc)2-Gln-Trp-Ala-Ala-PAla-His-Phe-Nle-NH2 (Doc)2-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2 -(Doc) 2-G1n-Trp-A1a-Va1-G1y-Hi s-Leu-Leu-NH2-(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 ipa_Gln_Trp_Ala_Val_ P Ala-H is_Leu_Leu_NH2-A印a' -A印a' -A印a' -A印a' -A印a' -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -A印a' -A印a' -A印a' -A印a' -A印a' -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -A印a' -A印a'(Doc)2-(Doc)2-(Doc)2-(Doc)2-(Doc)2-4-DPhe-4-DAla-4-DPhe-4-DPhe-4-DPhe-4_Aepa-4_Aepa-4_Aepa-4_Aepa-4_Aepa-(Doc)4-(Doc)4-(Doc)4-(Doc)4-(Doc)4-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2PAla-His-Phe-Nle-NH2 Gly-His-Leu-Leu-NH2 PAla-His-Leu-Nle-NH2 PAla-His-Leu-Leu-NH2 PAla-His-Phe-Nle-NH2 PAla-His-Phe-Nle-NH2 Gly-His-Leu-Leu-NH2-DAla-Gln-Trp-Ala-Val -DPhe-Gln-Trp-Ala-Val -DPhe-Gln-Trp-Ala-Val -DPhe-Gln-Trp-Ala-Val -DPhe-Gln-Trp-Ala-Ala -DAla-Gln-Trp-Ala-Val -DPhe-Gln-Trp-Ala-Val -DPhe-Gln-Trp-Ala-Val -DPhe-Gln-Trp-Ala-Val 4_Gln_Trp_Ala_Ala_ P Ala-His 4-Gln-Trp-Ala-Val-P Ala-His 4-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 4-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 4-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 4-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH: 4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH: 4_Aepa_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2 4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH: 4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu-NH: (Doc)4-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle-NH: (Doc)4-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH:PAla-His-Leu-Nle-P Ala_His_Leu_Leu-Phe-Nle_NH2 Phe-Nle-NH, NH2 -NH9—Aepa-(Doc)4--Gln--Trp--Ala--Val--Gly-His-Leu-Leu-NH2—Aepa-(Doc)4--Gln--Trp--Ala--Val-Ala-His-Leu-Nle-NH2—Aepa-(Doc)4--Gln--Trp--Ala--Val-Ala-His-Leu-Leu-NH2-(Doc)2-DPhe--Gln--Trp--Ala--Ala-Ala-His-Phe-Nle-NH2-(Doc)2-DAla--Gln--Trp--Ala--Val-Ala-His-Phe-Nle-NH2-(Doc)2-DPhe--Gln--Trp--Ala--Val--Gly-His-Leu-Leu-NH2-(Doc)2-DPhe--Gln--Trp--Ala--Val-Ala-His-Leu-Nle-NH2-(Doc)2-DPhe--Gln--Trp--Ala--Val-Ala-His-Leu-Leu-NH2-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH: -A印a-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH: -A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH: -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu-NH:—Aepa-(Doc)2--DPhe--Gln--Trp--Ala--Ala--PAla-His-Phe-Nle-NH2—Aepa-(Doc)2--DAla--Gln--Trp--Ala--Val--PAla-His-Phe-Nle-NH2—Aepa-(Doc)2--DPhe--Gln--Trp--Ala--Val--Gly-His-Leu-Leu-NH2—Aepa-(Doc)2--DPhe--Gln--Trp--Ala--Val--PAla-His-Leu-Nle-NH2—Aepa-(Doc)2--DPhe--Gln--Trp--Ala--Val-Ala-His-Leu-Leu-NH2-(Doc)2_Aepa--DPhe--Gln--Trp--Ala--Ala--PAla-His-Phe-Nle-NH2-(Doc)2_Aepa--DAla--Gln--Trp--Ala--Val--PAla-His-Phe-Nle-NH2-(Doc)2_Aepa--DPhe--Gln--Trp--Ala--Val--Gly-His-Leu-Leu-NH2-(Doc)2_Aepa--DPhe--Gln--Trp--Ala--Val--PAla-His-Leu-Nle-NH2-(Doc)2_Aepa--DPhe--Gln--Trp--Ala--Val-Ala-His-Leu-Leu-NH2-(Doc)2_Aepa--DPhe--Gln--Trp--Ala--Val--PAla-His-Ala-Nle-NH2-(Doc)2-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc)4-DPhe-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -(Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH2 -A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -(Doc)4-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -(Doc)4-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a- (Doc)4-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc)2-DPhe-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -(Doc)2-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -A印a- (Doc)2-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 _Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)-Thr-NH:-Aepa —N. HpGlu-His-Trp-Ser-Tyr -M""^ Leu-Arg-Pro-Gly-NH.-(Doc)2-Aepa —N'pGlu-His-Trp-Ser-Tyr — H"V" Leu-Arg-Pro-Gly-NH-(Doc)4-Aepa —NpGlu-His-Trp-Ser-Tyr-Leu-Arg-Pro-Gly-NH -Aepa-(Doc)4 —NpGlu-His-Trp-Ser-Tyr — Leu-Arg-Pro-Gly-NH<formula>formula see original document page 33</formula><formula>formula see original document page 34</formula><formula>formula see original document page 35</formula><formula>formula see original document page 36</formula>NHNJyu- (SA3-nqv-SAJ-dJJ,a-.!AVSA3) 0PA。-①IKCH3d①v」(。oa) IoHf N-AI90Jd-6」v-ns1ILl/^N-.^l-.5s-cl」l-s!工.nl9df!j-寸(ooa丫o工"工N-^lo-o」d-6JV-nsJ」>l--5s-d」l-s!H-n5do Hn(ooa)-O工工N-A一9p-d-6JV-ns,-JC^N—」Al-」3s-dJl-s!工-nlod工长鹏s X-V 60H6ZI0I N3_Doc_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2 -A印a- (Doc) 4-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: -A印a- (Doc) 3-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: -A印a- (Doc) 2-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: _Aepa_Doc_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2-(Doc)(「DPhe--cyclo(Cys--3ITyr_DTrp-丄ys--Thr-Cys)-Thr--NH2-(Doc)(「DPhe--cyclo(Cys--3ITyr_DTrp-丄ys--Thr-Cys)-Thr--NH2-(Doc);厂DPhe--cyclo(Cys--3ITyr_DTrp-丄ys--Thr-Cys)-Thr--NH2-(Doc),「DPhe--cyclo(Cys--3ITyr_DTrp-丄ys--Thr-Cys)-Thr--NH2-(Doc):「DPhe--cyclo(Cys--3ITyr_DTrp-丄ys--Thr-Cys)-Thr--NH2_(Doc)2-DPhe--cyclo(Cys--3ITyr_DTrp-丄ys--Thr-Cys)-Thr-—NH2_Doc_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _ (Aepa) 2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _ (Doc) 6_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH: _ (Doc) 5_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH: _ (Doc) 4_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH: _ (Doc) 3_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH: _ (Doc) 2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH: _Doc_Aepa_DPhe_cyclo (Cys_3ITyr_DT rp_Lys_Thr_Cys)_Thr_NH2 _Aepa_ (Doc) 4_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH: _Aepa_ (Doc) 3_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH: _Aepa_ (Doc) 2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH: _Aepa_Doc_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _ (Doc) 4_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH: -(Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -(Doc) 5-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -(Doc) 4-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -(Doc) 3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2 -(Doc) 2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2 _Doc_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Aepa) 2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 6_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 5_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 4_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 3_Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 2_Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH: _Doc_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2-Aepa_ (Doc) 4_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys) _Thr_NH2-Aepa_ (Doc) 3_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys) _Thr_NH2-Aepa_ (Doc) 2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys) _Thr_NH2-Aepa_Doc_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2-Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 4_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2-(Doc) 6_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 5_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 4_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 3_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 2_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2-Doc_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Aepa) 2_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 6_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 5_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 3_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 2_Aepa_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-Doc_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 6_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 5_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 4_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 3_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 2_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-Doc_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-Doc_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 2_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 5_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 6_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 6_Lys_DTyr_DTyr_cyclo(Gys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-Aepa- (Doc) 3_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2-Aepa- (Doc) 2_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2-Aepa_Doc_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-Aepa- (Doc) 4_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-Aepa- (Doc) 3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-Aepa— (Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2一Aepa-Doc-Lys-DTyr一-DTyr-cyclo(Cys-Tyr-DTrp-hys-Abu-Cys)一Thr-Nt{，-一Aepa-DPhe-cyclo(Cys一3ITyr-OTrp-Lys一-Abu-Cys)一Thr-NH，一OPhe-cyclo(Cys一3ITyr-DTrp-Lys-Abu-Cys)一Thr-Ng，一(Doc)．一Aepa一-DPho-cyclo(Cys一3ITyr-DTrp-Lys-Abu-Cys)一Thr-NH，一(,Aepa)，一Caeg-cyclo(DCys一3Pal-DTrp-Lys-DCys)一Thr(Bzl)一Tyr-NH，一(Doc)s-Aepa-Caeg-cyclo(DCys一3Pal-DTrp-Lys-DCys)一Thr(Bzl)一Tyr-Ng，一(Doc)s-Aepa-Caeg-cyclo(DCys一3Pal-DTrp-Lys-DCys)一Thr(Bzl)一Tyr-Ng，一(Doc)．一Aepa-Caeg-cyclo(DCys一3Pal-DTrp-Lys-OCys)一Thr(Bzl)一Tyr-Ng，一(Doc)，一Aepa-Caeg-cyclo(DCys一3Pal-DTrp-Lys-OCys)一Thr(Bzl)一Tyr-Ng，一(Doc)，一Aepa-Caeg-cyclo(DCys一3Pal-DTrp-Lys-OCys)一Thr(Bzl)一Tyr-Ng，一Ooc-Aepa-Caeg-cyclo(DCys一3Pal-DTrp-Lys-DCys)一Thr(Bzl)一Tyr-Ng，一(Doc)s-Caeg-cyclo(DCys一3Pal-OTrp-Lys-DCys)一Thr(Bzl)一Tyr-Nit，,一(Doc)s-Caeg-cyclo(DCys一3Pal-OTrp-Lys-DCys)一Thr(Bzl)一Tyr-Nit，,一(Doc)．一Caeg-cyclo(DCys一3Pal-OTrp-Lys-DCys)一Thr(Bzl)一Tyr-Nit，,一(Doc)，一Caeg-cyclo(DCys一3Pal-OTrp-Lys-DCys)一Thr(Bzl)一Tyr-Nit，,一(Doc)，一Caeg-cyclo(DCys一3Pal-OTrp-Lys-DCys)一Thr(Bzl)一Tyr-Nit，,一Ooc-Caeg-cyclo(DCys一3Pal一-DTrp-Lys一-DCys)一Thr(Bzl)一Tyr-Nit，,-一Aepa-Doc-Caeg-cyclo(DCys一3Pal-DTrp-Lys-DCys)一Thr(Bzl)一Tyr-Ng，-一Aepa一(Doc)，一Caeg-cyclo(DCys一3Pal-DTrp-Lys-DCys)一Thr(Bzl)一Tyr-Ng，-一Aepa一(Doc)，一Caeg-cyclo(DCys一3Pal-DTrp-Lys-DCys)一Thr(Bzl)一Tyr-Ng，-一Aepa一(Doc)．一Caeg-cyclo(DCys一3Pal-DTrp-Lys-DCys)一Thr(Bzl)一Tyr-Ng，一(Doc)s-Aepa-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys一-Abu-Cys)一Thr-Nt{，一(Doc)．一Aepa-Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrp-Lys一-Abu-Cys)一Thr-Nt{，-一Aepa一(Doc)．一-DPho-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)一Thr-Ng，-一Aepa-DPho-cyclo(Cys-Tyr-OTrp-Lys一-Abu-Cys)一Thr-Nit，,一(Doc)，一Aepa一-DPho-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)一Thr-Ng，一(Doc)．一Aepa一-DPho-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)一Thr-Ng，一(Doc)s-Aepa一-DPho-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)一Thr-Ng，一(,Aepa)，一DPho-cyclo(Cys-Tyr一-DTrp-Lys一-Abu-Cys)一Thr-NH，一(Doc)，一Aepa一-DPho-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)一Thr-Ng，一(Doc)．一Aepa一-DPho-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)一Thr-Ng，一(Doc)s-Aepa一-DPho-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)一Thr-Ng，一(Doc)s-Aepa一-DPho-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)一Thr-Ng，一(,Aepa)HSDAVF／DNY／RLRKOMAVKKLLNS I LN-Ng一(,Aepa)HSDAVF／DNY／RLRKOMAVKKALNS I LN-Ng一(,Aepa)HSDAVF／DNY／RLRKOMAVKKFLNS I LN-Ng一(,Aepa)HSDAVF／DNY／RLRKOMAVKKYLNS I LN-Ng一(,Aepa)HSDAVFTDNYTRLRKQ(NIo)AVKKYLNSILN一-hH，-一ttSDAVFTDNYTRLRKQMAVKKLLNS I LN-一NH-HSDAVFTDNYTRLRKQMAVKKALNSILN_NH2 -HSDAVFTDNYTRLRKQMAVKKFLNSILN_NH2 -HSDAVFTDNYTRLRKQMAVKKYLNSILN_NH2 -HSDAVFTDNYTRLRKQ(Nle)AVKKYLNSILN_NH2-Aepa-Caeg-cyclo(DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2_ (Doc) 4-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH:-(A印a) HSDGIFTDSYSRYRKQMA (A5c) KKYLAAVLGKRYKQRVKNK_NH2-(A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVLGKRYKQR (A6c) KNK_NH2-(A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVL (Ava) KRYKQRVKNK_NH2-(A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVL ( P Ala) KRYKQRVKNK_NH2-HSDGIFTDSYSRYRKQMA(A5c)KKYLAAVLGKRYKQRVKNK_NH2-HSDGIFTDSYSRYRKQMAVKKYLAAVLGKRYKQR (A6c) KNK_NH2-HSDGIFTDSYSRYRKQMAVKKYLAAVL(Ava)KRYKQRVKNK_NH2-HSDGIFTDSYSRYRKQMAVKKYLAAVL(P Ala)KRYKQRVKNK_NH2_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 6_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 4_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 6_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 6-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2_ (A印a) 2_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2-(Doc) 6-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2_ (A印a) 2_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_ (Doc) 6_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_ (Doc) 4_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 2_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_(Doc)6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_Aepa_ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-Aepa-Caeg-cyclo(DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2_ (Doc) 4-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2_ (Doc) 6-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2<formula>formula see original document page 41</formula>-Doc-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Doc-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -Doc-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -Doc-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Doc-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Doc-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Doc-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -Doc-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 -Doc-A印a-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-Doc-A印a-DPhe-Gln-Trp-Ala-Val- P Ala_His_Leu_Nle_NH2 -Doc-A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -A印a- (Doc) 3-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH: -A印a- (Doc) 3-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH: -A印a- (Doc) 3-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a- (Doc) 3-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH: -A印a- (Doc) 3-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu-NH: -(Doc) 3-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -(Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH2-(Doc) 3-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH2 -(Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2 -A印a-Doc-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 -A印a-Doc-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-A印a-Doc-DPhe-Gln-Trp-Ala-Val- P Ala_His_Leu_Nle_NH2-A印a-Doc-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2-(Doc) 4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-(Doc) 4-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-A印a-(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-(Doc) 4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-(Doc) 4-A印a-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu-NH:-A印a-(Doc)4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu-NH:-(Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2_ (Doc) 4_Aepa_Gaba_Gln_Trp_Ala_Val_ P Ala_His_Leu_Leu_NH2-A印a- (Doc) 4-Gaba-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2-(Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2_ (Doc) 4-A印a-Gaba-Gln-Trp-Ala-Va1- P Ala_His-Leu_Nle_NH2-A印a- (Doc) 4-Gaba-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2-A印a-Gln-Trp-Ala-Val- P Ala_His_Leu_Leu_NH2-A印a- (Doc) 2-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2-A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-A印a- (Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2-A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2-(Doc)2-Gln-Trp-Ala-Ala-PAla-His-Phe-Nle-NH2-(Doc)2-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2-(Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2-A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-(Doc) 4-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-(Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH2-(Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2-A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2-A印a- (Doc) 4-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -(Doc) 4-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -(Doc)4-DAla-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2 -(Doc) 4-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 4-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -(Doc) 4-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc) 4-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -(Doc) 4-A印a-DAla-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH2 -(Doc) 4_Aepa_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2 -(Doc) 4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle_NH2 -(Doc) 4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2 -A印a- (Doc) 4-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 4-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 4-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a- (Doc) 4-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -A印a- (Doc) 4-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -(Doc)4-Gln-Trp-Ala-Ala-PAla-His-Phe-Nle-NH2 -(Doc)4-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2 -(Doc) 4-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -(Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc) 4-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -(Doc) 4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH2 -A印a-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2(Doc)2_DPhe--Gln_Trp--Ala--Val(Doc)2_DPhe--Gln_Trp--Ala--Val(Doc)2_DPhe--Gln_Trp--Ala--Val(Doc)2_DAla--Gln_Trp--Ala--Val(Doc)2_DPhe--Gln_Trp--Ala--Ala<formula>formula see original document page 43</formula>-(Doc) 2-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -(Doc)2-DAla-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 _ (Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -A印a-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH: -(Doc) 2-A印a-DAla-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH: -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH: -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu-NH: -A印a- (Doc)2-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a-Gln-Trp-Ala-Val-Ala-His-Ala-Nle-NH2 -(Doc)2-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-N H2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH: -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -(Doc)2-DPhe-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -A印a- (Doc)4-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH: -(Doc)2-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc)4-DPhe-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -(Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH: -A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH: -(Doc)4-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -(Doc)4-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 _Aepa_Doc_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2 -A印a-Doc-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -A印a-Doc-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -A印a- (Doc) 3-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 3-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 3-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a- (Doc) 3-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -A印a- (Doc) 3-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -(Doc)3-Gln-Trp-Ala-Ala-PAla-His-Phe-Nle-NH2 -(Docx) 3-Gln-Trp-Ala-Val-P Ala-His-Phe—Nle—NH2 -(Doc) 3-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 3-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -(Doc) 3-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-A印a-Doc-Gln-Trp-Ala-Ala- P Ala_His-Phe-Nle_NH2 -A印a-Doc-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -(Doc) 3-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 3-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH: -(Doc) 3-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu-NH: -(Doc) 3-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -(Doc)3-DAla-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2 -(Doc) 3-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 3-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 _ (Doc) 3-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -Doc-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Doc-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -Doc-A印a-Gln-Trp-Ala-Ala- P Ala_His-Phe-Nle_NH2 -Doc-A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 _Doc_Aepa_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2 -Doc-A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -Doc-A印a-Gln-Trp-Ala-Val- P Ala—His-Leu-Leu_NH2—N HpGlu-His-Trp-Ser-Tyr一N HLeu-Arg-Pro-Gly-NH:<formula>formula see original document page 46</formula><formula>formula see original document page 47</formula><formula>formula see original document page 48</formula><formula>formula see original document page 49</formula><formula>formula see original document page 50</formula>_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:-(Doc) 4-A印a-DPhe-cydo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2_Doc_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2-(Doc) 2-A印a-DPhe-cydo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2-(Doc) 3-A印a-DPhe-cydo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2-(Doc) 5-A印a-DPhe-cydo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2-(Doc) 6-A印a-DPhe-cydo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2-(A印a) 2-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2-Doc-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 2-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 5-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-A印a- (Doc) 4-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2-A印a- (Doc) 3-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2-A印a- (Doc) 2-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2_Aepa_Doc_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2_ (Doc) 6_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 5_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 4_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 3_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_Doc_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Aepa) 2_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 6_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH2_ (Doc) 5_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 3_Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_Doc_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _Aepa_ (Doc) 4_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH: _Aepa_ (Doc) 3_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH: _Aepa_ (Doc) 2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH: _Aepa_Doc_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _ (Doc) 4_Aepa_DPhe_cycio(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH: _Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2-(Doc),「DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Thr--Cys)-Thr--NH2-(Doc)(「DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Thr--Cys)-Thr--NH2-(Doc)(「DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Abu--Cys)-Thr--NH2-(Doc)(厂DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Abu--Cys)-Thr--NH2-(Doc),「DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Abu--Cys)-Thr--NH2-(Doc):「DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Abu--Cys)-Thr--NH2_(Doc)2-DPhe--cycio (Cys--3ITyr--DTrp-丄ys--Abu--Cys)-Thr-—NH2_Doc_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Aepa) 2_DPhe_cy clo (Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 6_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH:_ (Doc) 5_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH:_ (Doc) 3_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH:_ (Doc) 2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH:_Doc_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_ (Doc) 4_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys) _Thr_NH:_Aepa_ (Doc) 3_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys) _Thr_NH:_Aepa_ (Doc) 2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys) _Thr_NH:_Aepa_Doc_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH:_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 4-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2-(Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2_ (Doc) 6_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_ (Doc) 5_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 3_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 2_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_Doc_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Aepa) 2_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 6_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 5_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 3_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 2_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Doc_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Aepa) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_ (Doc) 6_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 5_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 3_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 2_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_Doc_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc)4_Aepa--Gln--Trp--Ala--Val-Ala-His-Phe-Nle-NH2-(Doc)4_Aepa--Gln--Trp--Ala--Val--Gly-His-Leu-Leu-NH2-(Doc)4_Aepa--Gln--Trp--Ala--Val-Ala-His-Leu-Nle-NH2-(Doc)4_Aepa--Gln--Trp--Ala--Val-Ala-His-Leu-Leu-NH2-A印a-(Doc)4--Gln--Trp--Ala--Ala-Ala-His-Phe-Nle-NH2-A印a-(Doc)4--Gln--Trp--Ala--Val-Ala-His-Phe-Nle-NH2-A印a-(Doc)4--Gln--Trp--Ala--Val--Gly-His-Leu-Leu-NH2-A印a-(Doc)4--Gln--Trp--Ala--Val-Ala-His-Leu-Nle-NH2-A印a-(Doc)4--Gln--Trp--Ala--Val-Ala-His-Leu-Leu-NH2-(Doc) 4-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle_NH2 -(Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle_NH2 -(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle_NH2 -(Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc)4-A印a-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 _ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 5_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 2_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _Doc_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Aepa_ (Doc) 4_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2 _Aepa_ (Doc) 3_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2-Aeioa-(Doc)，-DPhe—cyclo(Cys—Tyr—DTrio—Lys—Abu—Cys)-Thr—NH，-Aeioa—Doc—DPhe—cyclo(Cys—Tyr—DTrio—Lys—Abu—Cys)-Thr—NH，-Aeioa-(Doc)．-Lys—DTyr—DTyr—cyclo(Cys—Tyr—DTrio—Lys—Abu—Cys)-Thr—NH，-Aeioa-(Doc)，-Lys—DTyr—DTyr—cyclo(Cys—Tyr—DTrio—Lys—Abu—Cys)-Thr—NH，-Aeioa-(Doc)，-Lys—DTyr—DTyr—cyclo(Cys—Tyr—DTrio—Lys—Abu—Cys)-Thr—NH，-Aeioa—Doc—Lys—DTyr—DTyr—cyclo(Cys—Tyr—DTrio—Lys—Abu—Cys)-Thr—NH，-(Doc)／；-Aeioa—Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH2-(Doc)．-Aeioa—Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-Aeioa—Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-(Doc)．-Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-(Doc)s—Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-(Aeioa)，-Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-(Doc)s—Aeioa—Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-(Doc)s—Aeioa—Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-(Doc)．-Aeioa—Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-(Doc)，-Aeioa—Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-(Doc)，-Aeioa—Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-Doc—Aeioa—Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-(Doc)s—Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-(Doc)s—Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-(Doc)．-Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-(Doc)，-Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-(Doc)，-Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-Doc—Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-Aeioa-(Doc)．-Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-Aeioa-(Doc)，-Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-Aeioa-(Doc)，-Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，-Aeioa—Doc—Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NH，<formula>formula see original document page 53</formula>Aeioa-(Doc)-Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NHAeioa—Caeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NHCaeg—cyclo(DCys-3Pal—DTrio—Lys—DCys)-Thr(BZl)-Tyr—NHAeioa-(Doc)-DPhe—cyclo(Cys-3ITyr—DTrio—Lys—Val—Cys)-Thr—NH(Doc)+-Aeioa—DPhe—cyclo(Cys-3ITyr—DTrio—Lys—Val—Cys)-Thr—NH_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH: -DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:-A印a- (Doc) 2-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH: -Aepa-Caeg-cyclo(DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2 -Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 -A印a- (Doc) 2-DPhe_cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 -(Doc) 4-A印a-DPhe-cydo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2 _Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2 -DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc)2-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle-NH: -(Doc)2-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH: -(Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH: -(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu-NH: -A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 一A印a-Gln-Trp-Ala-Val- P Ala_His_Leu_Leu_NH2-A印a- (Doc) 2-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -(Doc)2-Gln-Trp-Ala-Ala-PAla-His-Phe-Nle-NH2 -(Doc)2-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2 -(Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala_His_Leu_Leu_NH2Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH: DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH: DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH: DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu-NH: DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH: DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH: DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH: DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu-NH: -(Doc)4-Gln-Trp-Ala-Ala-PAla-His-Phe-Nle-NH2 -(Doc)4-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2 -(Doc) 4-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH255Aepa—(Doc) 2Aepa—(Doc) 2Aepa—(Doc) 2Aepa—(Doc) 2Aepa—(Doc) 2Aepa—(Doc) 2(Doc)4_DPhe(Doc)4_DAla(Doc)4_DPhe(Doc)4_DPhe(Doc)4_DPhe(Doc)4—A印a(Doc)4—A印a(Doc)4—A印a(Doc)4—A印a(Doc)4—A印aAepa—(Doc)4Aepa—(Doc)4Aepa—(Doc)4Aepa—(Doc)4Aepa—(Doc)4(Doc (Doc (Doc (Doc (Doc (Doc (Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2「A印a--Gln--Trp--Ala--Ala「A印a--Gln--Trp--Ala--Val「A印a--Gln--Trp--Ala--Val「A印a--Gln--Trp--Ala--Val「A印a--Gln--Trp--Ala--Val(Doc)4--Gln--Trp--Ala--Val(Doc)4--Gln--Trp--Ala--Ala(Doc)4--Gln--Trp--Ala--Val(Doc)4--Gln--Trp--Ala--Val(Doc)4--Gln--Trp--Ala--Val-A印a- (Doc -A印a- (Doc -A印a- (Doc -A印a- (Doc -A印a- (Doc-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala_His_Leu_Leu_NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2-A印a-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-N H2 -(Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc)2-DAla-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2 -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH2 -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 2-A印a-DAla-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH2 -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -A印a- (Doc)2-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -(Doc)2-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -(Doc)2-DPhe-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -A印a- (Doc)4-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2-(Doc)4-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2-(Doc)4-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2-A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2-(Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH2-(Doc)4-DPhe-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2-(Doc)2-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2-(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH2-A印a- (Doc) 4-Gaba-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2-(Doc) 4_Aepa_Gaba_Gln_Trp_Ala_Val_ P Ala_His_Leu_Leu_NH2-A印a-(Doc)4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-(Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-(Doc) 4-A印a-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-(Doc) 4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-A印a-(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-(Doc) 4-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-(Doc) 4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-A印a- (Doc) 4_Gaba_Gln_Trp_Ala_Val_ P Ala_His_Leu_Nle_NH2-(Doc) 4-A印a-Gaba-Gln-Trp-Ala-Va1- P Ala_His-Leu_Nle_NH2-(Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2<formula>formula see original document page 58</formula><formula>formula see original document page 59</formula><formula>formula see original document page 60</formula>-(Doc)广N-4 HpGlu-His-Trp-Ser-Tyr—y^_Leu_Arg_pro_Gly_NH_H-Aepa — NpGlu-His-Trp-Ser-Tyr—N^V"Leu-Arg-Pro-Gly-NH2H 『O-(Doc)2-Aepa — NpGlu-His-Trp-Ser-Tyr 、N^^Leu-Arg-Pro-Gly-Nh^H OH-(Doc)3-Aepa —NpGiu-His-Trp-Ser-Tyr-^j^ii^Leu-Arg-Pro-Gly-NH^H OH-(Doc)4-Aepa — NpGlu-His-Trp-Ser-Tyr—jj^"Leu-Arg-Pro-Gly-NH:M O-Aepa-Doc—NpGlu-His-Trp-Ser-Tyr —N^pLeu-Arg-Pro-Gly-NHsH OH-A印a-(Doc)2-Ns^pGlu-His-Trp-Ser-Tyr—N"^"Leu-A""g-Pr。-G'y-NH2<formula>formula see original document page 62</formula>-HSDGIFTDSYSRYRKQMAVKKYLAAVL(P Ala)KRYKQRVKNK-NH2-HSDGIFTDSYSRYRKQMAVKKYLAAVL(Ava)KRYKQRVKNK-NH2-HSDGIFTDSYSRYRKQMAVKKYLAAVLGKRYKQR (A6c) KNK-NH2-HSDGIFTDSYSRYRKQMA (A5c) KKYLAAVLGKRYKQRVKNK-NH2-(A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVL ( P Ala) KRYKQRVKNK_NH2-(A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVL (Ava) KRYKQRVKNK_NH2-(A印a) HSDGIFTDSYSRYRKQ丽KKYLAAVLGKRYKQR (A6c) KNK_NH2-(A印a) HSDGIFTDSYSRYRKQMA (A5c) KKYLAAVLGKRYKQRVKNK_NH2-A印a-Doc-Caeg-cyclo (DCys—3Pal_DTrp-Lys_DCys) —Thr (Bzl) _Tyr_NH2-A印a- (Doc) 2-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH:-A印a- (Doc) 3-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH:-A印a- (Doc) 4-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH:-(Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2-(Doc) 4-A印a-DPhe-cydo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2_Doc_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2-(Doc)厂A印a-DPhe-cycl0 (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2-(Doc) 3-A印a-DPhe-cydo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2-(Doc) s-A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2-(Doc) 6-A印a-DPhe-cydo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2-(A印a) 2-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2-Doc-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 5-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2_Aepa_Doc_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2-A印a- (Doc) 2-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2-A印a- (Doc) 3-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2-A印a- (Doc) 4-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2_Doc_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 3_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 5_Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 6_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (A印a) 2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH2_Doc_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 3_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 4_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 5_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 6_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_Aepa_Doc_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_Aepa_ (Doc) 2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH2_Aepa_ (Doc) 3_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH2_Aepa_ (Doc) 4_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH2_ (Doc) 6_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH2_ (Doc) 4_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 4_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_Doc_Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 3_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 5_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 6_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Aepa) 2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Doc_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2-(Doc) 3-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2-(Doc) 4-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2-(Doc) 5-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2-(Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)_Thr_NH2_Aepa_Doc_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys) _Thr_NH2_Aepa_ (Doc) 2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys) _Thr_NH2_Aepa_ (Doc) 3_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys) _Thr_NH2-A印a- (Doc) X4-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) -Thr-NH:-(Doc) 6-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2-(Doc) 4-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 6_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_ (Doc) 4_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Aepa) 2_ (Doc) 2_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_Aepa_Doc_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Aepa) 2_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 2_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_(Aepa) 2_ (Doc) 4_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_ (Doc) 6_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_ (Doc) 2_Aepa_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_Aepa_ (Doc) 4_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 6_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 2_ (Aepa) 2_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_Doc_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 2_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 3_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 5_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 6_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Aepa) 2_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Doc_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 2_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 3_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_ (Doc) 4_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 5_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 6_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_Doc_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 2_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_ (Doc) 3_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_ (Doc) 4_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_ (Doc) 5_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_ (Doc) 6_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_ (Aepa) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Doc_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 5_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_Doc_Lys__DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_ (Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_Aepa_ (Doc) 3_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_Aepa_ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_Aepa_Doc_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_ (Doc) 2_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH:_Aepa_ (Doc) 3_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH:_Aepa_ (Doc) 4_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH:<formula>formula see original document page 67</formula><formula>formula see original document page 68</formula><formula>formula see original document page 69</formula><formula>formula see original document page 70</formula>_ (Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 8_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Aepa_ (Doc) 2_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Aepa) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 2_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 4_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH: _ (Doc) 6_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _Aepa_ (Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _Aepa_ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _Aepa_ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH: _Lys_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2<formula>formula see original document page 71</formula>_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Aepa_Lys_DTyr_DTyr_(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 2_Aepa_Lys_DTyr_DTyr_(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Aepa_ (Doc) 2_Aepa_Lys_DTyr_DTyr_(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 6_Aepa_Lys_DTyr_DTyr_(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Doc_Aepa_Doc_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2<formula>formula see original document page 71</formula>_ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Doc_Aepa_Lys_DTyr_DTyr_(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 2_Aepa_Lys_DTyr_DTyr_(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 3_Aepa_Lys_DTyr_DTyr_(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 4_Aepa_Lys_DTyr_DTyr_(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Aepa_Doc_Aepa_Lys_DTyr_DTyr_(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Doc_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2<formula>formula see original document page 72</formula>(Doc)+一Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrio-Lys-Abu-Cys)一Lys-DTyr-DTyr-cyclo(Cys-Tyr-DTrio-Lys-Abu-Cys)一Thr-NH<formula>formula see original document page 72</formula>一(Doc)s-Caeg-cyclo(DCys一3Pal-DTrio-Lys-DCys)一Thr(BZl)一Tyr-NH一(Doc)d-Caeg-cyclo(DCys一3Pal-DTrio-Lys-DCys)一Thr(BZl)一Tyr-NH一Caeg-cyclo(DCys一3Pal-DTrio-Lys-DCys)一Thr(BZl)一Tyr-NH一Aeioa-Caeg-cyclo(DCys一3Pal-DTrio-Lys-DCys)一Thr(BZl)一Tyr-NH一(Doc)d-Aeioa-Caeg-cyclo(DCys一3Pal-DTrio-Lys-DCys)一Thr(BZl)一Tyr-NH一(Doc)s-Aeioa-Caeg-cyclo(DCys一3Pal-DTrio-Lys-DCys)一Thr(BZl)一Tyr-NH一Caeg-cyclo(DCys一3Pal-DTrio-Lys-DCys)一Thr(BZl)一Tyr-NH一Aeioa-Caeg-cyclo(DCys一3Pal-DTrio-Lys-DCys)一Thr(BZl)一Tyr-NH一Doc-Aeioa-Caeg-cyclo(DCys一3Pal-DTrio-Lys-DCys)一Thr(BZl)一Tyr-NH一(Doc)，一Aeioa-Caeg-cyclo(DCys一3Pal-DTrio-Lys-DCys)一Thr(BZl)一Tyr-NH一(Doc)，一Aeioa-Caeg-cyclo(DCys一3Pal-DTrio-Lys-DCys)一Thr(BZl)一Tyr-NH一(Doc)+一Aepa-Caeg-cyclo(DCys一3Pal-DTrp-Lys-DCys)一Thr(BZl)一Tyr-NH，一(Doc)s-Aeioa-Caeg-cyclo(DCys一3Pal-DTrio-Lys-DCys)一Thr(BZl)一Tyr-NH一(Doc)s-Aeioa-Caeg-cyclo(DCys一3Pal-DTrl~一Lys-DCys)一Thr(BZl)一Tyr-NH一(Aeioa)一Caeg-cyclo(DCys一3Pal-DTrio-Lys-DCys)一Thr(BZl)一Tyr-NH一Doc-Caeg-cyclo(DCys一3Pal-DTrio-Lys-DCys)一Thr(BZl)一Tyr-NH一(Doc)，一Caeg-cyclo(DCys一3Pal-DTrio-Lys-DCys)一Thr(BZl)一Tyr-NH一(Doc)，一Caeg-cyclo(DCys一3Pal-DTrio-Lys-DCys)一Thr(BZl)一Tyr-NH一(1)oc)d-Caeg-cyclo(1)Cys一3Pal-1)Trio-Lys-1)Cys)一Thr(1321)一Tyr-Nit一(Doc)s-Caeg-cyclo(DCys一3Pal-DTrio-Lys-DCys)一Thr(BZl)一Tyr-NH一(Doc)s-Caeg-cyclo(DCys一3Pal-DTrio-Lys-DCys)一Thr(BZl)一Tyr-NH一(Aeioa)一(Doc)2-DPhe-cyclo(Cys-Tyr-DTrio-Lys-Abu-Cys)一Thr-NH一Aeioa-Doc-Aeioa-DPhe-cyclo(Cys-Tyr-DTrio-Lys-Abu-Cys)一Thr-NH一(Aeioa)一DPhe-cyclo(Cys-Tyr-DTrio-Lys-Abu-Cys)一Thr-NH一Doc-Aeioa-Doc-Aeioa-DPhe-cyclo(Cys-Tyr-DTrio-Lys-Abu-Cys)一Thr-NH一(Doc)，一DPhe-cyclo(Cys-Tyr-DTrio-Lys-Abu-Cys)一Thr-NH一(Aeioa)2--(Doc)d-DPhe-cyclo(Cys-Tyr-DTrio-Lys-Abu-Cys)一Thr-NH_Aepa_ (Doc) 6_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2 _ (Doc) 2_Aepa_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2 _Aepa_ (Doc) 4_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 6_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 2_ (Aepa) 2_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2 -HSDAVFTDNYTRLRKQ(Nle)AVKKYLNSILN_NH2 -HSDAVFTDNYTRLRKQMAVKKYLNSILN_NH2 -HSDAVFTDNYTRLRKQMAVKKFLNSILN_NH2 -HSDAVFTDNYTRLRKQMAVKKALNSILN_NH2 -HSDAVFTDNYTRLRKQMAVKKLLNSILN_NH2 -(A印a) HSDAVFTDNYTRLRKQ (Nle) AVKKYLNSILN_NH2 -(A印a) HSDAVFTDNYTRLRKQMAVKKYLNS ILN-NH2 -(A印a) HSDAVFTDNYTRLRKQMAVKKFLNS ILN-NH2 -(A印a) HSDAVFTDNYTRLRKQMAVKKALNS ILN-NH2 -(A印a) HSDAVFTDNYTRLRKQMAVKKLLNS ILN-NH2_Aepa_ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 2_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 8_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2 _Aepa_ (Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Aepa) 2_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 2_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 4_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 6_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH: _Aepa_ (Doc) 2_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _Aepa_ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _Aepa_ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _Lys_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-A印3-Lys-DTyr-DTyr-cycle (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_ (Doc) 2_Aep3_Lys_DTyr_DTyr_cycle(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_ (Doc) 2_Aep3_Lys_DTyr_DTyr_cycle(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_ (Doc) 6_Aep3_Lys_DTyr_DTyr_cycle(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 2_Aep3_Lys_DTyr_DTyr_cycle(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Doc_Aep3_Lys_DTyr_DTyr_cycle(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 3_Aep3_Lys_DTyr_DTyr_cycle(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Aep3_Lys_DTyr_DTyr_cycle(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2一A印3-Doc-A印3-Lys-DTyr-DTyr-cycle (Cys_Tyr_DTrp_Lys_Abu_Cys) -Thr-NH:-Doc-DPhe-Gln-T rp-Ala-Val-PAla-His-Leu-Leu-N H2-Doc-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-Doc-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-Doc-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2-Doc-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2-Doc-A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2-Doc-A印a-DPhe-Gln-Trp-Ala-Val- P Ala_His_Leu_Nle_NH2-Doc-A印a-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-Doc-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2-A印a- (Doc) 3-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu-NH:-A印a- (Doc) 3-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH:-A印a- (Doc) 3-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-A印a- (Doc) 3-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH:-A印a- (Doc) 3-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH:-(Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2-(Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH2-(Doc) 3-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-(Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH2-(Doc) 3-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2-A印a-Doc-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2-A印a-Doc-DPhe-Glri-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2-A印a-Doc-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-A印a-Doc-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2-A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2-A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2-A印a- (Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-A印a- (Doc) 2-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2-A印a-Gln-Trp-Ala-Val- P Ala_His_Leu_Leu_NH2-A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2-A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2-A印a- (Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-A印a- (Doc) 2-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2-A印a-Gln-Trp-Ala-Val- P Ala_His_Leu_Leu_NH2-A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2-(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-(Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-(Doc)2-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2-(Doc)2-Gln-Trp-Ala-Ala-PAla-His-Phe-Nle-NH2-A印a- (Doc) 4-Gaba-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2_ (Doc) 4_Aepa_Gaba_Gln_Trp_Ala_Val_ P Ala_His_Leu_Leu_NH2-(Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-A印a-(Doc)4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu-NH:-(Doc) 4-A印a-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu-NH:-(Doc) 4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-A印a-(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-(Doc) 4-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-(Doc) 4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-A印a- (Doc) 4-Gaba-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2 _ (Doc) 4-A印a-Gaba-Gln-Trp-Ala-Va1- P Ala_His-Leu_Nle_NH2 -(Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2OOHO ODoc--DPhe--Gln--Trp-Ala-Val-P Ala--His--Leu--Leu--NH2Doc--DPhe--Gln--Trp-Ala-Val-P Ala--His--Leu--Nle--NH2Doc--DPhe--Gln--Trp-Ala-Val-Gly-His-Leu-Leu-NH2Doc--DAla--Gln--Trp-Ala-Val-P Ala--His--Phe--Nle--NH2Doc--DPhe--Gln--Trp_Ala_Ala_P Ala--His--Phe--Nle--NH2Aepa—Gln--Trp--Ala-Ala-PAla-His--Phe--Nle-—NH2-(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu-NH: -(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH: -(Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc)2-Gln-Trp-Ala-Val-e Ala-His-Phe-Nle-NH: -(Doc)2-Gln-Trp-Ala-Ala-e Ala-His-Phe-Nle-NH:—Aepa—(Doc)4--DPhe_Gln_Trp_Ala_Val_ P Ala_His_Leu_Leu--NH2—Aepa—(Doc)4--DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle--NH2—Aepa—(Doc)4--DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2—Aepa—(Doc)4--DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle--NH2—Aepa—(Doc)4--DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle--NH2-(Doc)4_Aepa--DPhe_Gln_Trp_Ala_Val_ P Ala_His_Leu_Leu--NH2-(Doc)4_Aepa--DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle--NH2-(Doc)4_Aepa--DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-(Doc)4_Aepa--DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle--NH2-(Doc)4_Aepa--DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle--NH2-(Doc)4-DPhe--Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-(Doc)4-DPhe--Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-(Doc)4-DPhe--Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-(Doc)4-DAla--Gln-Trp Ala-Val-P Ala-His-Phe-Nle-NH2-(Doc)4-DPhe--Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2—Aepa—(Doc)4--Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2—Aepa—(Doc)4--Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2—Aepa—(Doc)4--Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2—Aepa—(Doc)4--Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2-A印a- (Doc) 4-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -(Doc) 4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2 -(Doc) 4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle_NH2 _ (Doc) 4_Aepa_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2 -(Doc) 4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH2 -(Doc) 4-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 -(Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -(Doc) 4-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc)4-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2 -(Doc)4-Gln-Trp-Ala-Ala-PAla-His-Phe-Nle-NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu-NH: -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH: -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a- (Doc) 2-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH: -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH: -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 _ (Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc)2-DAla-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu-NH: -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH: -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 2-A印a-DAla-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH: -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH: -A印a- (Doc)2-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -(Doc)2-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH: -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -(Doc)2-DPhe-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -A印a- (Doc)4-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc)4-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2-(Doc)4-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2-A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH:-(Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH:-(Doc)4-DPhe-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2-(Doc)2-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2-(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH:-A印a- (Doc) 3-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2-A印a- (Doc) 3-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2-A印a- (Doc) 3-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-A印a- (Doc) 3-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-A印a- (Doc) 3-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2-A印a-Doc-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2-A印a-Doc-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2_Aepa_Doc_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2-A印a-Doc-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-A印a-Doc-Gln-Trp-Ala-Ala- P Ala_His-Phe-Nle_NH2-(Doc) 3-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-(Doc) 3-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-(Doc) 3-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-(Doc)3-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2-(Doc)3-Gln-Trp-Ala-Ala-PAla-His-Phe-Nle-NH2-(Doc) 3-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu-NH:-(Doc) 3-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH:-(Doc) 3-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2_ (Doc) 3-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-(Doc) 3-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-(Doc) 3-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-(Doc)3-DAla-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2-(Doc) 3-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2-Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-Doc-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-Doc-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2-Doc-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2-Doc-A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2-Doc-A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2_Doc_Aepa_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2-Doc-A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-Doc-A印a-Gln-Trp-Ala-Ala- P Ala_His-Phe-Nle_NH2-(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -(Doc -A印a--A印a--A印a--A印a--A印a--(Doc) -(Doc) -(Doc) -A印a--A印a--A印a--A印a--A印a-OH —2-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle--DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2-NH9(Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 (Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 (Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 (Doc)4-Gln-Trp-Ala-Val-eAla-His-Phe-Nle-NH2 (Doc)4-Gln-Trp-Ala-Ala-PAla-His-Phe-Nle-NH2 「A印a-Gln-Trp-Ala-Val- P Ala_His_Leu_Leu_NH2 fA印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 4_Aepa_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2 (Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 (Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 (Doc)2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 (Doc)2-DAla-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2 (Doc) 2-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala_His_Leu_Leu_NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2-A印a-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-(Doc) 2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-(Doc)2-DAla-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2-(Doc) 2-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2-(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2-(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH2-(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-(Doc) 2-A印a-DAla-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH2-(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2-A印a- (Doc)2-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2-A印a-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2-(Doc)2-Gln-Trp-Ala-Val-e Ala-H is-Ala-Nle_NH2-A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2-A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2-(Doc)2-DPhe-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2-A印a- (Doc)4-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2-(Doc)4-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2-(Doc)4-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2-A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2-(Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH2-(Doc)4-DPhe-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2-(Doc)2-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2-(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH2-A印a- (Doc) 3-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2-A印a- (Doc) 3-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2-A印a- (Doc) 3-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-A印a- (Doc) 3-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-A印a- (Doc) 3-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2-A印a-Doc-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2-A印a-Doc-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2_Aepa_Doc_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2-A印a-Doc-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-A印a-Doc-Gln-Trp-Ala-Ala- P Ala_His-Phe-Nle_NH2-(Doc) 3-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-(Doc) 3-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-(Doc) 3-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-(Doc)3-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2-(Doc)3-Gln-Trp-Ala-Ala-PAla-His-Phe-Nle-NH2-(Doc) 3-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2-(Doc) 3-A印a-DPhe-G ln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH:-(Doc) 3-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH: _ (Doc) 3-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc) 3-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -(Doc) 3-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc)3-DAla-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2 -(Doc) 3-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Doc-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Doc-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -Doc-A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -Doc-A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 _Doc_Aepa_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2 -Doc-A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -Doc-A印a-Gln-Trp-Ala-Ala- P Ala_His-Phe-Nle_NH2pGlu-His-Trp-Ser-Tyr-Aepa — N HpG lu-H is-Trp-Ser-TyrN "^x^Leu-Arg-Pro-NHEt-(Doc)2-Aepa—N-HpGlu-His-Trp-Ser-Tyr —N^pLeu-Arg-Pro-NHEt -Aepa-(Doc)2—HpGlu-His-Trp-Ser-Tyr — N^^Leu-Arg-Pro-NHEt-Aepa 一N一 p HpGlu-His-Trp-Ser-Tyr—N^pLeu—Arg-Pr<>Gly-NH2-(Doc)2-Aepa —N-HpGlu-His-Trp-Ser-Tyr —j^^YLeu-Arg-Pro-Gly-NH2-(Doc)3-Aepa —N_ HpGlu-His-Trp-Ser-Tyr —H X-(Doc)4-Aepa—N-HpGlu-His-Trp-Ser-Ty r - NM^^Leu-Arg-Pro-Gly-NHs-Aepa-Doc— J^-pGlu-His-Trp-Ser-Tyr — N^|pLeu-Arg-Pra-Gly-NH2<formula>formula see original document page 83</formula>-Aepa-(Doc)4—N-HpGlu-His-Trp-Ser-His—g、TrP-Tyr-pro-G|y.NH，-Aepa—N-HpGlu-His-Trp-Ser-His—N^Y丁rp-Tyr-Pro-Gly-NH2-(Doc)2-Aepa —N-HpGlu-His-Trp-Ser-His—N"^pTrp-Tyr-Pro-Gly-NH2-Aepa-(Doc)2—y-HpGlu-His-Trp-Ser-His —y^YTrp-Tyr-Pro-Gly-NH,H O-Aepa —N一HpGlu-His-Trp-Ser-Tyr — H^pLeu-Arg-Pro-Gly-NH2-(Doc),-Aepa—N-HpGlu-His-Trp-Ser-Tyr-N^Y~Leu-Arg-Pro-Gly-NH2-(DocVA印a —&HpGlu-His-Trp-Ser-Tyr-N"^^ipLeu-Arg-Pro-Gly-NH2-(Doc)4-Aepa—N-HpGlu-His-Trp-Ser-Tyr-Jj^YLeu-Arg-Pro-Gly-NH2<formula>formula see original document page 85</formula>pGlu-His-Trp-Ser-Tyr—N^Y"Leu-Arg-Pro-Gly-NH2H o-(Doc)2 — [;j-pGlu-His-Trp-Ser-Tyr—jj^^Leu-Arg-Pro-Gly-NHsH S'(Doc)3卞 HpGlu-His-Trp-Ser-Tyr—n "^^Leu-Arg-Pro-Gly'H JT-NH,O-(Doc)4 —pGlu-His-Trp-Ser-Tyr —g^YLel>Arg—Pro-Gly-NH2-Doc—y-HpGlu-His-Trp-Ser-Tyr—N^^Leu-Arg-Pra-Gly陽NH2H i-(Doc)2 —[J HpG lu-His-Trp-Ser-Ty r—N Leu-Arg-Pro-Gly-N H2 -(Doc)3—flpGlu-His-Trp-Ser-Tyr-N^vLeu-Arg-Pro-Gly-NH2H f-(Doc)广[lpGlu-His-Trp-Ser-Tyr—^j^YLeu-Arg-Pro-Gly-NH2OA H -Aepa — NpGlu-His-Trp-Ser-Tyr—N^pLeu-Arg-Pro-Gly-NH2H0H-(Doc)2-Aepa —N^^pGlu-His-Trp-Ser-Tyr 1 &a' 2H-(Doc)3-Aepa —pGlu-His-Trp-Ser-Tyr—N^pLeu-Arg-Pro-Gly-NHaH oH-(Doc)4-Aepa —pGlu-His-Trp-Ser-Tyr — N^^Leu-Arg-Pro-Gly-NH H-Aepa-Doc —NpGlu-His-Trp-Ser-Tyr-N^pLeu陽Arg-Pro-Gly隱NH2HoH-Aepa-(Doc)2 —NpGlu-His-Trp-Ser-Tyr — N"^Leu-Arg-Pra-Gly-NH2H-Aepa-(Doc)3 —N^^pGlu-His-Trp-Ser-Tyr —N^YLeu-Arg_PrcH3ly—NH2-Aepa-(Doc)4 — NpGlu-His-Trp-Ser-Tyr —N^^^pLeu-Arg-Pro-Gly-NHz -Doc —MpGlu-His-Trp-Ser-Tyr-g^Leu-Arg-Pro匿Gly-NH2 -(Doc)2—HpGlu-His-Trp-Ser-Tyr — N^pLeu-Arg-Pro-Gly-NHsH O-(Doc)3—npGlu-His-Trp-Ser-Tyr —N^pLeu-Arg-Pro-Gly-NH^-(Doc)4 — NpGlu-His-Trp-Ser-Tyr — g^YLeu-Arg-Pro-Gly-NH2O-A印a- (Doc) 4_DPhe_Gln_Trp_Ala_Val_ P Ala_His_Leu_Leu_NH2 -A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a- (Doc) 4-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -(Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2 -(Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH2 -(Doc) 4-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 4-A印a-DAla-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH2 -(Doc)HSDGIFTDSYSRYRKQMAVKKYLAAVL(P Ala)KRYKQRVKNK_NH2 -(Doc)HSDGIFTDSYSRYRKQMAVKKYLAAVL(Ava)KRYKQRVKNK_NH2 -(Doc) HSDGIFTDSYSRYRKQMAVKKYLAAVLGKRYKQR (A6c) KNK_NH2 -(Doc) HSDGIFTDSYSRYRKQMA (A5c) KKYLAAVLGKRYKQRVKNK_NH2 -(A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVL ( P Ala) KRYKQRVKNK_NH2-(A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVL (Ava) KRYKQRVKNK_NH2-(A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVLGKRYKQR (A6c) KNK_NH2-(A印a) HSDGIFTDSYSRYRKQMA (A5c) KKYLAAVLGKRYKQRVKNK_NH2-(Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2-(Doc) 4-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH:-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2<formula>formula see original document page 89</formula>-A印a- (Doc) 4-Gaba-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2_ (Doc) 4_Aepa_Gaba_Gln_Trp_Ala_Val_ P Ala_His_Leu_Lau_NH2-(Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-A印a-(Doc)4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu-NH:-(Doc) 4-A印a-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu-NH:-(Doc) 4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-A印a-(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-(Doc) 4-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-(Doc) 4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2 <formula>formula see original document page 89</formula>06o工工oHfN->ICI-0」d-6」v,nel^^N-」A.L-.ss-d」l-s!H-nlsd,H—寸(。oa丫oTT 工NHN->le>-o」d-6JV-nent/\NI」Al-」ss-d」l-s!H-nl9d-H-f 丫OIT 工,H」(ooa丫o"工N^一s-o」d-6JV-nsl-lc/^N —」Al-」as-d」l-s!工.n一od工-N—8a-oHf N二一90」d-6」v-nsJL^N-」Al,J3s-dJl-s!工-nl9d工Nl寸(ooa)-oNHN->lo-o」d-6」v-n9--^/^HI.IAl-.ss-dJl-s!H-n5d-H」(。oa)，0工f N-AI92d老-ns,-Ll/^N —」>i-」3s-d」l-s!H-nlod<formula>formula see original document page 91</formula>-Doc —SpGlu-His-T，Ser-Ty—M Leu-Arg-Pro-G'y-NH2H O-(Doc)2—[jpGlu-His-Trp-Ser-Tyr —N^pLeu-Arg-Pro-Gly-Nh^H OH陽(Doc)3—NpGlu-His-Trp-Ser-Tyr —N^pLeu-Arg-Pm-G'y-NHsH OH-(Doc)4—NpGlu-His-Trp-Ser-Tyr - N'H—eu-Arg-Pro-Gly-NH2O-A印a- (Doc) 4-Gaba-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2-(Doc) 4-A印a-Gaba-Gln-Trp-Ala-Va1- P Ala_His-Leu_Nle_NH2-(Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-Aepa—N-HpGlu-His-Trp-Ser-Tyr—^j""^pLeu-Arg-Pro-Gly-NH2-(Doc),Aepa — N-HpGlu-His-Trp-Ser-Tyr—N'Hleu-Arg-Pro-Gly-NH2O<formula>formula see original document page 93</formula><formula>formula see original document page 94</formula><formula>formula see original document page 95</formula>-(Doc) 3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 -(Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 -(Doc) 5-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 -(Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2 _Doc_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2 -(Doc)厂A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: -(Doc) 3-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: -(Doc) 「A印a-DPhe-cycl0 (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: -(Doc) e-A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: -(A印a) 2-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2_Aepa_Doc_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2 -A印a- (Doc) 2-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: -A印a- (Doc) 3-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: -A印a- (Doc) 4-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH: _Doc_Aepa_DPhe_cyclo(Cys_3ITyDTrp_Lys_Thr_Cys)_Thr_NH2 _ (Doc) 2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH: _ (Doc) 3_Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH: _ (Doc) 5_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH: _ (Doc) 6_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH: _ (A印a) 2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH2 _Doc_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2(Doc)2_DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Thr--Cys)-Thr--NH2(Doc):「DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Thr--Cys)-Thr--NH2(Doc),「DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Thr--Cys)-Thr--NH2(Doc);厂DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Thr--Cys)-Thr--NH2(Doc)(「DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Thr--Cys)-Thr--NH2(Doc)(「DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Thr--Cys)-Thr--NH2(Doc),「DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Thr--Cys)-Thr-—NH2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _ (Doc) 4_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH: _DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2O OOH O<formula>formula see original document page 97</formula>-(Doc)4-Aepa-Gaba—N-HpGlu-His-Trp-Ser-Tyr—N""^Leu-Arg-Pro-Gly-NH2H-Aepa-(Doc)4-Gaba —n-HOpGlu-His-Trp-Ser-Tyr--(Doc)4-Gaba —N-H-N' H-Leu-Arg-Pro-Gly-NH2OpGlu-His-Trp-Ser-Tyr -口'-(Doc)4-Aepa-Gaba —N-Leu-Arg-Pro-Gly-NH2OpGlu-His-Trp-Ser-Tyr 、N^pLeu墨Arg-Pro-Gly-NH2H O-Aepa-(Doc)4-Gaba — npGlu-His-Trp-Ser-Tyr、N Leu-Arg-Pra—G'y-NH2H OH-(Doc)4-Gaba—NpGlu-His-Trp-Ser-Tyr 、 Leu-Arg-Pro-Gly-NH2H OOOH O O_ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_ (Doc) 4_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2DPhe-cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Aepa_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 2-A印a-DPhe-cydo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2-(Doc) 2-A印a-DPhe-cydo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2_ (Doc) 2-A印a-Caeg-cycl。 (DCys-3Pal-DTrp-Lys-DCys) _Thr (Bzl) _Tyr_NH2_ (Doc) 4-A印a-Caeg-cycl。 (DCys-3Pal-DTrp-Lys-DCys) _Thr (Bzl) _Tyr_NH2_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 2-A印a-DPhe-cydo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2_ (Doc) 2-A印a-Caeg-cycl。 (DCys-3Pal-DTrp-Lys-DCys) _Thr (Bzl) _Tyr_NH2_ (Doc) 4-A印a-Caeg-cycl。 (DCys-3Pal-DTrp-Lys-DCys) _Thr (Bzl) _Tyr_NH2_Doc_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 2_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 3_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 5_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 6_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa) 2_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Doc_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 2_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 3_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_ (Doc) 4_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 5_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 6_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_Doc_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 2_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_ (Doc) 3_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_ (Doc) 4_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_ (Doc) 5_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_ (Doc) 6_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_ (A印a) 2_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_Doc_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 5_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aep3_Doc_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_ (Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_Aepa_ (Doc) 3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_Aepa_ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_Aepa_Doc_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_ (Doc) 2_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_Aepa_ (Doc) 3_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_Aepa_ (Doc) 4_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_ (Doc) 6-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2_ (Doc) 4-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)_Th r(Bzl)_Tyr_NH2-Aepa-Caeg-cyclo(DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2_ (Doc) 4-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2_ (Doc) 4-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)_Th r(Bzl)_Tyr_NH2-Aepa-Caeg-cyclo(DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2Doc_Aep3_Caeg_cyclo (DCys_3P 3l_DTrp_Lys_DCys)_Th r(Bzl)_Tyr_NH2_ (Doc) 2-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2_ (Doc) 3-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2_ (Doc) 4-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2_ (Doc) s-A印a-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2_ (Doc) 6-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2_ (A印a) 2-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2Doc-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2_ (Doc) 2-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2_ (Doc) 3-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2_ (Doc) 4-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2_ (Doc) 5-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2_ (Doc) 6-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2_Aep3_Doc_Caeg_cyclo(DCys—3Pal—DTrp—Lys—DCys)_Thr(Bzl)_Tyr_NH2-A印a- (Doc) 2-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2-A印a- (Doc) 3-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2-A印a- (Doc) 4-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc)厂A印a-DPhe-cycl0 (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2_ (Doc) 2-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2-A印a- (Doc) 4-Gaba-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2-(Doc) 4-A印a-Gaba-Gln-Trp-Ala-Va 1_ P Ala-His-Leu-Nle_NH2-(Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-(Doc)4-Aepa-Gaba —N-HpG I u-H is-Trp-Ser-Ty r — Leu-Arg-Pro-G ly-N H2-Aepa-(Doc)4-Gaba — N-HpGlu-His-Trp-Ser-Tyr—y^^Leu.A Pro—G| NH-(Doc)4-Gaba —N-HpGlu-His-Trp-Ser-Tyr—^j^pLeu-Arg—pro_G|y-NH2O-(Doc^-Aepa-Gaba—f^ ,户，u. t e t"ii -Leu-Arg-Pro-Gly-NH2 pGlu-H旧-Trp-Ser-Tyr一口 ^ 。 J 2-Aepa-(Doc)4-Gaba — NpGlu-His-Trp-Ser-Tyr — N^li~Leu-Arg-Pro-Gly-NH2H OH-(Doc)4-Gaba —pGlu-His-Trp-Ser-Tyr — N LeU-Arg-Pr。-Gly-NH2H O-(Doc)HSDAVFTDNYTRLRKQ(Nle)AVKKYLNSILN-NH2-(Doc)HSDAVFTDNYTRLRKQMAVKKYLNSILN-NH2-(Doc)HSDAVFTDNYTRLRKQMAVKKALNSILN-NH2-(Doc)HSDAVFTDNYTRLRKQMAVKKLLNSILN-NH2-(A印a) HSDAVFTDNYTRLRKQ (Nle) AVKKYLNSILN_NH2-(A印a) HSDAVFTDNYTRLRKQMAVKKYLNS ILN-NH2-(A印a) HSDAVFTDNYTRLRKQMAVKKALNS ILN-NH2-(A印a) HSDAVFTDNYTRLRKQMAVKKLLNS ILN-NH2-A印a- (Doc) 2-Gln—Trp-Ala-Val- P Ala—His-Leu-Leu_NH2-Aepa-(Doc)4 -J^|-G|P-His-TrP-Ser-His1^"Trp Gly-NH2-(Doc) 2-A印a-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr ( P zl) _Tyr-NH20=Coi、0 o o-Aepa- (Doc)4-Gaba_Gln-Trp-Ala-Val-0 Ala-His-Leu-Nle-NH2 -(Doc) 4-A印a-Gaba-Gln-Trp_Ala_Val_ g Ala_His_Leu_Nle_NH2-(Doc)4-Aepa-Gaba—N-HpGlu-His-Trp-Ser-Tyr -[j^pLeu-Arg-Pro-Giy-Ni^O-Aepa-(Doc)4-Gaba — N-HpGlu-His-Trp-Ser-Tyr — H^VLeu-Arg-Pro-Gly-NH2<formula>formula see original document page 104</formula>.HN-AIO-p-d-eJV-naJIU/^a—」>x-Jes-d」l-s!H-nlE>d-Aepa-(Doc)2 — N HGlp-His-Trp-Ser-Ty r — N Leu-Arg-Pro-G ly-NH.H O-A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala_His_Leu_Leu_NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -(A印a) 2- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -(A印a) 2- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -Doc-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -Doc-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Doc-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Doc-DAla-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Doc-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -Doc-A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -Doc-A印a-DPhe-Gln-Trp-Ala-Val- P Ala_His_Leu_Nle_NH2-Doc-A印a-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -Doc-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 -A印a- (Doc) 3-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -A印a- (Doc) 3-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -A印a- (Doc) 3-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a- (Doc) 3-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 3-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -(Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2 -(Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH2 -(Doc) 3-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH2 -(Doc) 3-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -A印a-Doc-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -A印a-Doc-DPhe-Gln-Trp-Ala-Val- P Ala_His_Leu_Nle_NH2-A印a-Doc-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-Doc-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 -A印a- (Doc) 4-Gaba-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -(Doc) 4-A印a-Gaba-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu_NH2-(Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-A印a-(Doc)4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-(Doc) 4-A印a-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-(Doc) 4-Gaba-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-A印a- (Doc) 4-Gaba-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle_NH2_ (Doc) 4-A印a-Gaba-Gln-Trp-Ala-Va1- P Ala_His-Leu_Nle_NH2-(Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-A印a-(Doc)4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-(Doc) 4-A印a-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2-(Doc) 4-Gln-Trp-Ala-Val-Gly-His-Leu-W (CH2NH) -Leu_NH2O-A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala—His—Leu—Leu—NH:O_ (Doc) 4-A印a-Gaba-Gln-Trp-Ala-Va1- P Ala_His-Leu_Nle_NH:-(Doc) 4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH2-(Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH:O_ (Doc) 4-A印a-Gaba-Gln-Trp-Ala-Va1- P Ala_His-Leu_Nle_NH: -(Doc) 4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH2 -(Doc) 4-Gaba-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -(Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH:O-Sue- (Doc) 3-A印a-Gaba-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH: -Suc-A印a- (Doc) 3-Gaba-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle-NH: -Suc-A印a- (Doc) 3-Gln-Trp-Ala_Val- P Ala-His-Leu-Nle-NH2 -Sue- (Doc) 3-A印a-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH2 -Sue- (Doc) 3-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -Suc-A印a- (Doc) 3-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH: -Sue- (Doc) 3-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH:<formula>formula see original document page 108</formula>-A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -A印a- (Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a- (Doc) 2-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 2-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 ipa_Gln_Trp_Ala_Val_ P Ala_His_Leu_Leu_NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2-A印a-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2-(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2-(Doc) 2-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2-(Doc) 2-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2-(Doc)2-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2-(Doc)2-Gln-Trp-Ala-Ala-PAla-His-Phe-Nle-NH2-A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2-A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2-A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2-A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2-A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2-A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2_ (A印a) 2- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu-NH:_ (A印a) 2- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH:—Aepa—(Doc)4--DPhe--Gln--Trp--Ala--Val-Ala-His-Leu-Leu-NH2—Aepa—(Doc)4--DPhe--Gln--Trp--Ala--Val--PAla-His-Leu-Nle-NH2—Aepa—(Doc)4--DPhe--Gln--Trp--Ala--Val--Gly-His-Leu-Leu-NH2—Aepa—(Doc)4--DAla--Gln--Trp--Ala--Val--PAla-His-Phe-Nle-NH2—Aepa—(Doc)4--DPhe--Gln--Trp--Ala--Ala--PAla-His-Phe-Nle-NH2-(Doc)4_Aepa--DPhe--Gln--Trp--Ala--Val-Ala-His-Leu-Leu-NH2-(Doc)4_Aepa--DPhe--Gln--Trp--Ala--Val--PAla-His-Leu-Nle-NH2-(Doc)4_Aepa--DPhe--Gln--Trp--Ala--Val--Gly-His-Leu-Leu-NH2-(Doc)4_Aepa--DAla--Gln--Trp--Ala--Val--PAla-His-Phe-Nle-NH2-(Doc)4_Aepa--DPhe--Gln--Trp--Ala--Ala--PAla-His-Phe-Nle-NH2-(Doc)4_Aepa--DPhe--Gln--Trp--Ala--Ala--PAla-His-Phe-Nle-NH2-(Doc)4-DPhe--Gln--Trp--Ala--Val-Ala-His-Leu-Leu-NH2-(Doc)4-DPhe--Gln--Trp--Ala--Val-Ala-His-Leu-Nle-NH2-(Doc)4-DPhe--Gln--Trp--Ala--Val--Gly-His-Leu-Leu-NH2-(Doc)4-DAla--Gln--Trp--Ala--Val-Ala-His-Phe-Nle-NH2-(Doc)4-DPhe--Gln--Trp--Ala--Ala-Ala-His-Phe-Nle-NH2-A印a-(Doc)4--Gln--Trp--Ala--Val-Ala-His-Leu-Leu-NH2-A印a-(Doc)4--Gln--Trp--Ala--Val-Ala-His-Leu-Nle-NH2-A印a-(Doc)4--Gln--Trp--Ala--Val--Gly-His-Leu-Leu-NH2-A印a-(Doc)4--Gln--Trp--Ala--Val-Ala-His-Phe-Nle-NH2-A印a-(Doc)4--Gln--Trp--Ala--Ala-Ala-His-Phe-Nle-NH2-(Doc)4_Aepa--Gln--Trp--Ala--Val-Ala-His-Leu-Leu-NH2-(Doc)4_Aepa--Gln--Trp--Ala--Val-Ala-His-Leu-Nle-NH2-(Doc)4_Aepa--Gln--Trp--Ala--Val--Gly-His-Leu-Leu-NH2-(Doc) 4-A印a-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH2 -(Doc) 4-A印a-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle_NH2 -(Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc) 4-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -(Doc) 4-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc)4-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2 -(Doc)4-Gln-Trp-Ala-Ala-PAla-His-Phe-Nle-NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu-NH: -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH: -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a- (Doc) 2-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH: -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH: -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a-DAla-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 _ (Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc)2-DAla-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2 -(Doc) 2-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu-NH: -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH: -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc) 2-A印a-DAla-Gln-Trp-Ala-Va1- P Ala-His-Phe-Nle-NH: -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH: -A印a- (Doc)2-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -A印a-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -(Doc)2-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -A印a- (Doc) 2-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH: -A印a-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH2 -(Doc)2-DPhe-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -A印a- (Doc)4-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc)4-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc)4-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2 -A印a- (Doc) 4-DPhe-Gln-Trp-Ala-Val- P Ala-His-Ala-Nle-NH: -(Doc) 4-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH: -(Doc)4-DPhe-Gln-Trp-Ala-Val-eAla-His-Ala-Nle-NH2-(Doc)2-A印a-Gln-Trp-Ala-Val-e Ala-His-Ala-Nle-NH2 -(Doc) 2-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Ala-Nle-NH: -A印a- (Doc) 3-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -A印a- (Doc) 3-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 -A印a- (Doc) 3-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -A印a- (Doc) 3-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a- (Doc) 3-Gln-Trp-Ala-Ala- P Ala-His-Phe-Nle-NH2 -A印a-Doc-Gln-Trp-Ala-Val- P Ala-His-Leu-Leu_NH2 -A印a-Doc-Gln-Trp-Ala-Val- P Ala-His-Leu-Nle-NH2 _Aepa_Doc_Gln_Trp_Ala_Val_Gly_His_Leu_Leu_NH2 -A印a-Doc-Gln-Trp-Ala-Val- P Ala-His-Phe-Nle-NH2 -A印a-Doc-Gln-Trp-Ala-Ala- P Ala_His-Phe-Nle_NH2 -(Doc) 3-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc) 3-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -(Doc) 3-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc)3-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2 -(Doc)3-Gln-Trp-Ala-Ala-PAla-His-Phe-Nle-NH2 -(Doc) 3-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Leu-NH: -(Doc) 3-A印a-DPhe-Gln-Trp-Ala-Va1- P Ala-His-Leu-Nle-NH: -(Doc) 3-A印a-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 _ (Doc) 3-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -(Doc) 3-DPhe-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -(Doc) 3-DPhe-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -(Doc)3-DAla-Gln-Trp-Ala-Val-PAla-His-Phe-Nle-NH2 -(Doc) 3-DPhe-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Leu_NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Leu-Nle-NH2 -Doc-Gln-Trp-Ala-Val-Gly-His-Leu-Leu-NH2 -Doc-Gln-Trp-Ala-Val-P Ala-His-Phe-Nle-NH2 -Doc-Gln-Trp-Ala-Ala-P Ala-His-Phe-Nle-NH2<formula>formula see original document page 112</formula><formula>formula see original document page 113</formula><formula>formula see original document page 114</formula>oHHN-/ 0Jd-6JV-ns.lLI/\_M—」>h-」9g-d」.L-s!H-nlc_dO H"工N.AI90」d-6」v-nsJ,J/ \z/ J>J.-J9s-ci.a.s!H-nl。dooHf N-^一9-0」d-6」v-3Jilt' jjNl」Al-」3s-d」l-s!工-nlodN— Bdav-H工。HN-AIO-o」d-6」v.s-- L/^pl JA.I.-J9s-d」l-s!H-nlodo工,N」(。oa丫"HN->l90」d-6」v-ns1J/^j;j_JAl-」3s-d」l-s!H-nlodoH—义ooa)-"HN么IQ-p-d-6JV-na,l,^^yl.-A.L-」9s-d」.L-s!工-nl3dO工-N— N(ooa丫工"HN.AI92d-pv-ns--L^ R—JAl-.5s-d」J.-s!H-nl9dII--N— .xooa)-5§n#长鹏s彰V 60H6ZI0I N3<formula>formula see original document page 116</formula>PGlu-His-Trp-Ser-Tyr —y^[pLeu-Arg-Pro-Gly-NH2H O-HSDGIFTDSYSRYRKQMAVKKYLAAVL(P Ala)KRYKQRVKNK_NH2-HSDGIFTDSYSRYRKQMAVKKYLAAVL(Ava)KRYKQRVKNK_NH2-HSDGIFTDSYSRYRKQMAVKKYLAAVLGKRYKQR (A6c) KNK_NH2-HSDGIFTDSYSRYRKQMA (A5c) KKYLAAVLGKRYKQRVKNK_NH2-(A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVL ( P Ala) KRYKQRVKNK_NH2-(A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVL (Ava) KRYKQRVKNK_NH2-(A印a) HSDGIFTDSYSRYRKQMAVKKYLAAVLGKRYKQR (A6c) KNK_NH2-(A印a) HSDGIFTDSYSRYRKQMA (A5c) KKYLAAVLGKRYKQRVKNK_NH2-(Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Var_Cys)_Thr_NH2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2-(Doc) 4-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH:-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2-Doc-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 3-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 4-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 5-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2-(Doc) 6-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Val-Cys)_Thr_NH2_Doc_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2_ (Doc) 2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH:_ (Doc) 3_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH:_ (Doc) 5_Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH:_ (Doc) 6_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH:-(A印a) 2-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2_Aepa_Doc_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Val_Cys)_Thr_NH2-A印a- (Doc) 2-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH:-A印a- (Doc) 3-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH:-A印a- (Doc) 4-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Val-Cys) -Thr-NH:_Doc_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH:_ (Doc) 3_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH:_ (Doc) 5_Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH: _ (Doc) 6_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH: _ (Aepa) 2_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH2 _Doc_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2(Doc) 2-DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Thr--Cys)-Thr--NH2(Doc) 3-DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Thr--Cys)-Thr--NH2(Doc) 4-DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Thr--Cys)-Thr--NH2(Doc) 5-DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Thr--Cys)-Thr--NH2(Doc) 6-DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Thr--Cys)-Thr--NH2(Doc) 6-DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Thr--Cys)-Thr--NH2(Doc) 4-DPhe--cyclo(Cys--3ITyr--DTrp-丄ys--Thr--Cys)-Thr-—NH2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _ (Doc) 4_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH: _DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2<formula>formula see original document page 119</formula><formula>formula see original document page 119</formula><formula>formula see original document page 119</formula><formula>formula see original document page 120</formula><formula>formula see original document page 121</formula><formula>formula see original document page 122</formula>-(Doc)4、nhO-Aepa-Lys_DTyr-DTyr-cyclo(Cys-Tyr_DTrp-Lys-Abu-Cys)-Thr_NH2-DPhe-cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH2-Aepa_Lys_DTyr_DTyr-cyclo(Cys_Tyr_DTrp_Lys-Abu-Cys)-Thr_NH2-Aepa_DPhe_cyclo(Cys-Tyr-DTrp_Lys_Abu_Cys)_Thr-NH2_ (Doc) 2-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH:_ (Doc) 4-A印a-Caeg-cycl。 (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH:O-Aep3_Lys_DTyr_DTyr_cyclo(Cys-Tyr-DTrp-Lys-Abu-Cys)-Thr-NH: -Doc_Aepa_DPhe_cyclo(Cys-3ITyr_DTrp_Lys_Abu-Cys)-Thr_NH2 -(Doc) 2-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys-Abu-Cys) -Thr_NH2 -(Doc) 3-A印a-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) -Thr-NH2 —(Doc) s-A印a-DPhe-cyclo (Cys—3ITyr_DTrp-Lys—Abu—Cys) —Thr_NH2 -(Doc) 6-A印a-DPhe-cycl。 (Cys-3ITyr-DTrp-Lys_Abu-Cys) _Thr_NH2 -(A印a) 2-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) -Thr_NH2 _Doc_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -(Doc) 2-DPhe-cyclo(Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr_NH2 -(Doc) 3-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys)-Thr-NH2-(Doc) 4-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2-(Doc) 5-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2-(Doc) 6-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2-(Doc) 6-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2-(Doc) 4-DPhe-cyclo (Cys-3ITyr-DTrp-Lys-Abu-Cys) _Thr_NH2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_ (Doc) 4_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_ (Doc) 4_Aepa_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_ (Doc) 4_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc) 2-A印a-DPhe-cydo (Cys-3ITyr-DTrp-Lys-Val-Cys) _Thr_NH2_ (Doc) 2-A印a-Caeg-cycl。 (DCys-3Pal-DTrp-Lys-DCys) _Thr (Bzl) _Tyr_NH2_ (Doc) 4-A印a-Caeg-cycl。 (DCys-3Pal-DTrp-Lys-DCys) _Thr (Bzl) _Tyr_NH2_Doc_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 2_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 3_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 5_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 6_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Aepa) 2_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Doc_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 2_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 3_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_ (Doc) 4_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 5_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 6_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2_Doc_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 2_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 3_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 4_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 5_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Doc) 6_Aepa_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _ (Aepa) 2_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Doc_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 5_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Aepa_Doc_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 _Aepa_ (Doc) 2_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _Aepa_ (Doc) 3_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _Aepa_ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH: _Aepa_Doc_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2 _Aepa_ (Doc) 2_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2 _Aepa_ (Doc) 3_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2 _Aepa_ (Doc) 4_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2 _ (Doc) 6-Caeg-cyclo(DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2 _ (Doc) 4-Caeg-cyclo(DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2 -Caeg-cyclo (DCys-3Pal-DTrp-Lys-DCys)-Thr(Bzl)_Tyr_NH2 _Aepa_Caeg_cyclo (DCys_3Pal_DTrp_Lys_DCys)_Thr(Bzl)_Tyr_NH2 _ (Doc) 4-A印a-Caeg-cycl。 (DCys-3Pal-DTrp-Lys-DCys) _Thr (Bzl) _Tyr_NH2 _ (Doc) 4-A印a-Caeg-cycl。 (DCys-3Pal-DTrp-Lys-DCys) _Thr (Bzl) _Tyr_NH2 -Caeg-cyclo (DCys-3Pal-DTrp-Lys-DCys)-Thr(Bzl)_Tyr_NH2 _Aepa_Caeg_cyclo(DCys_3Pal_DTrp_Lys_DCys)_Thr(Bzl)_Tyr_NH2 _Doc_Aepa_Caeg_cyclo(DCys_3Pal_DTrp_Lys_DCys)_Thr(Bzl)_Tyr_NH2 _ (Doc) 2-A印a-Caeg-cycl。 (DCys-3Pal-DTrp-Lys-DCys) _Thr (Bzl) _Tyr_NH2 _ (Doc) 3-A印a-Caeg-cycl。 (DCys-3Pal-DTrp-Lys-DCys) _Thr (Bzl) _Tyr_NH2 _ (Doc) 4-A印a-Caeg-cycl。 (DCys-3Pal-DTrp-Lys-DCys) _Thr (Bzl) _Tyr_NH2 _ (Doc) 5-A印a-Caeg-cycl。 (DCys-3Pal-DTrp-Lys-DCys) _Thr (Bzl) _Tyr_NH2 _ (Doc) 6-A印a-Caeg-cycl。 (DCys-3Pal-DTrp-Lys-DCys) _Thr (Bzl) _Tyr_NH2 _ (A印a) 2-Caeg-cyclo (DCys-3Pal-DTrp-Lys-DCys) _Thr (Bzl) _Tyr_NH2 -Doc-Caeg-cyclo(DCys-3Pal-DTrp-Lys-DCys)-Thr(Bzl)_Tyr_NH2 _ (Doc) 2-Caeg-cyclo (DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2 _ (Doc) 3-Caeg-cyclo(DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2_ (Doc) 4-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2_ (Doc) 5-Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2_ (Doc) 6-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2_Aep3_Doc_Caeg_cyclo(DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2-A印a- (Doc) 2-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2-A印a- (Doc) 3-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2-A印a- (Doc) 4-Caeg-cyclo (DCys_3Pal-DTrp-Lys_DCys) -Thr (Bzl) _Tyr_NH2-HSDAVFTDNYTRLRKQ(Nle)AVKKYLNSILN_NH2-HSDAVFTDNYTRLRKQMAVKKYLNSILN_NH2-HSDAVFTDNYTRLRKQMAVKKALNSILN_NH2-HSDAVFTDNYTRLRKQMAVKKLLNSILN_NH2-(A印a) HSDAVFTDNYTRLRKQ (Nle) AVKKYLNSILN_NH2-(A印a) HSDAVFTDNYTRLRKQMAVKKYLNS ILN-NH2-(A印a) HSDAVFTDNYTRLRKQMAVKKALNS ILN-NH2-(A印a) HSDAVFTDNYTRLRKQMAVKKLLNS ILN-NH2_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH:_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2-(Doc)厂A印a-DPhe-cycl0 (Cys-3ITyr-DTrp-Lys-Val—Cys) _Thr_NH2_ (Doc) 4_Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 6_DPhe_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_ (Doc) 4_Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 4_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 6_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 4_Aep3_Lys_DTyr_DTyr_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH:_ (Doc) 4_Lys_DTyr_DTyr_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2_ (Doc) 6_Lys_DTyr_DTyr_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2(Doc), (Doc), (Doc)f(Doc) (Doc) (Doc) (Doc) (Doc) (Doc) (Doc) (Doc) (Doc) (Doc) (Doc) (Doc) (Doc) (Doc) (Doc)-Aepa--Caeg--Caeg--Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 -eye lo (DCys-3Pal-DTrp-Lys-DCys)-Thr(Bzl)_Tyr_NH2 -cyclo (DCys-3Pal-DTrp-Lys-DCys)—Thr(Bzl)_Tyr_NH2-Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -Aepa_DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 -DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 -DPhe_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 -Aep3_Lys_DTyr_DTyr_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 -Lys_DTyr_DTyr_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 -Lys_DTyr_DTyr_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 -Aepa-Caeg-cyclo (DCys-3Pal-DTrp-Lys-DCys)_Thr(Bzl)_Tyr_NH2 -Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)-Thr(Bzl)_Tyr_NH2 -Caeg-cyclo(DCys_3Pal-DTrp-Lys_DCys)—Thr(Bzl)_Tyr_NH2-Suc_ (Doc): -Suc_(Doc): -Suc_ (Doc); -Suc_(Doc): -Suc_ (Doc).-Aepa_DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -DPhe_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -Aep3_Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2 -Lys_DTyr_DTyr_cyclo(Cys_Tyr_DTrp_Lys_Abu_Cys)_Thr_NH2_Suc_ (Doc) 5_Lys_DTyr_DTyr_cyclo (Cys_Tyr_DTrp_Lys_Abu_Cys) _Thr_NH2 _Suc_ (Doc) 3_Aepa_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _Suc_ (Doc) 3_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH2 _Suc_ (Doc) 5_DPhe_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH2 _Suc_ (Doc) 3_Aepa_Lys_DTyr_DTyr_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys) _Thr_NH2 _Suc_ (Doc) 3_Lys_DTyr_DTyr_cyclo (Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _Suc_ (Doc) 5_Lys_DTyr_DTyr_cyclo(Cys_3ITyr_DTrp_Lys_Thr_Cys)_Thr_NH2 _Suc_ (Doc) 3_Aepa_Caeg_cyclo(DCys_3Pal_DTrp_Lys_DCys)_Thr(Bzl)_Tyr_NH2 _Suc_ (Doc) 3_Caeg_cyclo (DCys_3Pal_DTrp_Lys_DCys)_Thr(Bzl)_Tyr_NH2 _Suc_ (Doc) 5_Caeg_cyclo (DCys_3Pal_DTrp_Lys_DCys)_Thr(Bzl)_Tyr_NH2 _Suc_ (Doc) 4_Caeg_cyclo (DCys_3Pal_DTrp_Lys_DCys)_Thr(Bzl)_Tyr_NH2 _Suc_ (Doc) 5_Aepa_Caeg_cyclo(DCys_3Pal_DTrp_Lys_DCys)_Thr(Bzl)_Tyr_NH2 _Suc_ (Doc) 4_Aepa_Caeg_cyclo(DCys_3Pal_DTrp_Lys_DCys)_Thr(Bzl)_Tyr_NH2
22. —种包括有效量的权利要求1-21任意一项的化合物或其药学上可接受的盐以及 药学上可接受的载体的药物组合物。
23. —种在需要接受治疗的个体上治疗疾病的方法，所述方法包括给予所述个体治疗 有效量的权利要求1-21中任意一项的化合物或其药学上可接受的盐，其中所述疾病选自 纤维化、良性前列腺增生、动脉硬化、再狭窄、乳腺癌、结肠癌、胰腺癌、前列腺癌、肺癌、小细 胞肺癌、卵巢癌、表皮癌和血癌。
24. —种在需要接受治疗的个体上治疗疾病的方法，所述方法包括给予所述个体治疗 有效量的权利要求1-21中任意一项的化合物或其药学上可接受的盐，其中所述疾病选自 良性前列腺增生、再狭窄、乳腺癌、结肠癌、胰腺癌、前列腺癌、肺癌、小细胞肺癌、卵巢癌、表 皮癌和血癌。
25. —种在需要接受治疗的个体上治疗疾病的方法，所述方法包括给予所述个体治疗 有效量的权利要求1的化合物或其药学上可接受的盐，其中所述疾病的特征是表达了一种 或多种生长抑素型受体的不良细胞增生。
26. —种在需要接受治疗的个体上治疗疾病的方法，所述方法包括给予所述个体治疗 有效量的权利要求1的化合物或其药学上可接受的盐，其中所述疾病的特征是表达了一种 或多种铃蟾肽型受体的不良细胞增生。
27. —种在需要接受治疗的个体上治疗疾病的方法，所述方法包括给予所述个体治疗 有效量的权利要求1的化合物或其药学上可接受的盐，其中所述疾病的特征是表达了一种 或多种LHRH型受体的不良细胞增生。
全文摘要
本发明涉及肽载体，描述了靶向细胞毒化合物和与治疗肿瘤和其它疾病的医疗用途相关的方法。
文档编号A61K47/48GK101791409SQ20101000373
公开日2010年8月4日 申请日期2004年4月21日 优先权日2003年4月22日
发明者孙·H·金, 怡兰娜·沈, 珍妮·玛丽·科姆斯托克, 董正欣 申请人:研究及应用科学协会股份有限公司