黑皮质素治疗胰岛素敏感的应用的制作方法

专利名称：黑皮质素治疗胰岛素敏感的应用的制作方法
黑皮质素治疗胰岛素敏感的应用
背景技术：
黑皮质素属于调节肽家族，其通过激素原阿黑皮素原(P0MC ；131个氨基酸长)的 翻译后加工形成。P0MC被加工成三类激素黑皮质素、促肾上腺皮质激素，和多种内啡肽 (例如，促脂解素)(Cone 等人，Recent Prog. Horm. Res. ,51 :287_317，(1996) ；Cone 等人， Ann. N. Y. Acad. Sci.，31 :342_363，(1993))。迄今已经表征了五种黑皮质素受体(MC-R)。这些包括黑素细胞特异性受体 (MC1-R)、肾上腺皮质特异性ACTH受体(MC2-R)、黑皮质素_3 (MC3-R)、黑皮质素_4 (MC4-R) 和黑皮质素-5受体(MC5-R)。所有的黑皮质素受体都应答肽激素类别的促黑激素(MSH) (Cone 等人，Ann. N. Y. Acad. Sci.，680 :342_363 (1993) ；Cone 等人，Recent Prog. Horm. Res. ,51 :287-318(1996))。对黑皮质素受体(MC-R)作为设计用于治疗体重紊乱如肥胖和恶病质的新型 治疗剂的靶标存在极大的兴趣。其中一个受体，MC4-R，是332个氨基酸的跨膜蛋白，其 在脑以及胎盘和肠组织中表达(Cone等人，Ann. N. Y. Acad. Sci.，680 =342-363(1993)； Cone 等人，Recent Prog. Horm. Res. , 51 =287-318 (1996)) 最近的药理学证明已经确定 重要的MC4-R受体是分别为黑皮质素激动剂和拮抗剂报道的减食欲和促进食欲作用的 主要介体(Giraudo 等人，Brain Res.，809 302-306 (1998) ；Farooqi 等人，NE J Med.， 348 1085-1095 (2003) ；MacNeil 等人，Eu. J. Pharm. ,44 141-157 (2002) ；MacNeil 等人， Eu. J. Pharm.，450 :93_109(2002) ；Kask 等人，Neuroreport, 10 :707_711(1999) ；Chen 等 人，.Transgenic Res.，9 145-54, (2000) ；Marsh 等人，Nat Genet. ,21 :119_22，(1999)； Balthasar 等人，Cell, 123 :493_505 (2005))。体重紊乱的并发症一般包括不能产生和利用胰岛素，其常常导致不完善的葡萄糖 调节。不能适当控制葡萄糖代谢的结果影响整体健康的许多方面，包括能量代谢、神经病和 心脏病。当前受体选择性黑皮质素受体配体的进展证明黑皮质素受体(尤其是MC4-R)活 化作用在治疗葡萄糖调节(包括胰岛素代谢)中的治疗潜力。发明概述本发明涉及肽或其可药用盐治疗罹患胰岛素抵抗的哺乳动物的应用，所述肽是一 种或更多种黑皮质素受体(MC-R)的配体。在一个实施方案中，所述配体是黑皮质素4受体 的激动剂。在一个优选的实施方案中，所述黑皮质素受体配体是根据本文中描述的通式的 配体或选自本文中描述的特定的肽。胰岛素抵抗受试者哺乳动物可能肥胖或超重，其可能由于服用本发明的肽而体重 减轻。胰岛素抵抗受试者哺乳动物也可能是正常体重或偏瘦。受试者哺乳动物的胰岛素抵 抗状态可不依赖于体重减轻而进行治疗。此外，受试者哺乳动物可以是任何年龄的人类受 试者，如婴儿、儿童、成人或老人。在第一实施方案中，本发明提供治疗哺乳动物受试者的胰岛素抵抗的方法(伴随 或不伴随体重减轻)，通过施用治疗有效量的根据通式(I)的黑皮质素受体4配体及其可药 用盐、水合物、溶剂化物或前药(见公开号为W02007/008704国际专利申请，此处整体引用作为参考)(R2R3) -A'-c (A2-A3-A4-A5-A6-A7-A8-A9) -A^-R1(I)其中A1 是 Acc、HN- (CH2) m_C (0)、L_ 或 D_ 氨基酸或缺失；A2 ^ Cys> D-Cys> hCys> D-hCys> Pen> D-Pen> Asp ^ Glu ；A3 是 Gly、Ala、3-Ala、Gaba、Aib、D_ 氨基酸或缺失;八4是圯8、2-卩&1、3-卩&1、4-卩&1、1&2、2-111士、3-111土或(X1，X2，X3，X4，X5) Phe ；A5 是 D-PheiD-l-NaLDUaLD-TrpJ-BaLD-G1，X2，X3，X4，X5) Phe、L_Phe 或 D-(Et)Tyr ；八6是八印、11八印、0&13、0&口、1^8、0111或 HN-CH((CH2)n-N(R4R5))-C(0)；八7是11印、1-恥1、2-恥1、8&1、81 、0-11印、0-1-恥1、0-2-恥1、0-8&1或 D_Bip ；A8 是 Gly、D_Ala、Acc、Ala、3-Ala、Gaba、Apn、Ahx、Aha、HN_ (CH2) S_C (0)或缺失；A9 是 Cys> D-Cys> hCys、D_hCys、Pen、D_Pen、Dab、Dap、Orn 或 Lys ；A10 是 Acc、HN- (CH2) t_C (0)、L_ 或 D_ 氨基酸或缺失；R1 是-OH 或-NH2 ；R2和R3各自在每种情况下独立地选自H、(CfCj烷基、(CfCj杂烷基、(CfCj 酰基 、(C2-C30)火布基、(C2_C30)块基、方基(C「C30)焼基、方基(C「C30) 酰基、被取代的(Ci-Cj 烷基、被取代的(Ci-Cj杂烷基、被取代的(Ci-Cj酰基、被取代的(C2-CJ烯基、被取代的 (c2-c30)炔基、被取代的芳基(Ci-Cj烷基、和被取代的芳基(Ci-Cj酰基；R4和R5各自在每种情况下独立地是H、(CrC40)烷基、(CfC；。)杂烷基、(CfC；。)酰 基、(C2-C40)火布基、(C2_C40)块基、方基(C「C40)焼基、方基(C「C40) 酰基、被取代的(c「c40) 烷基、被取代的(Ci-Cj杂烷基、被取代的(Q-Cd酰基、被取代的(c2-c4(l)烯基、被取代的 (c2-c40)炔基、被取代的芳基(crc4Q)烷基、被取代的芳基(crc4Q)酰基、(Ci-Cj烷基磺酰 基或-c(nh)-nh2 ；m在每种情况下独立地是1、2、3、4、5、6或7;n在每种情况下独立地是1、2、3、4或5 ；s在每种情况下独立地是1、2、3、4、5、6或7;t在每种情况下独立地是1、2、3、4、5、6或7;^、^、^、义和^各自在每种情况下独立地是！^丄丨』!"、〗、(U烷基、被取代 的(Cho)烷基、(c2_10)烯基、被取代的(c2_10)烯基、(c2_10)炔基、被取代的(c2_10)炔基、芳 基、被取代的芳基、OH、NH2、N02或CN ；条件是(I).当R4是(Ci-Cj酰基、芳基(Ci-Cj酰基、被取代的(CrCj酰基、被取代 的芳基(Ci-C；。)酰基、(Ci-C；。)烷基磺酰基或-C(NH)-NH2时，那么R5是H或(Ci-C；。)烷基、 (c「c40)杂烷基、(c2-c40)烯基、(c2-c40)炔基、芳基(C「C40)烷基、被取代的(CfQo)烷基、 被取代的(Ci-Cj杂烷基、被取代的(c2-c4(l)烯基、被取代的(c2-c4(l)炔基或被取代的芳基 (C「C40)焼基；(II).当R2为(Q-CJ酰基、芳基(Q-CJ酰基、被取代的(Q-CJ酰基、或被取代的芳基(C「C30)酰基时，则R3是H、(CrC30)烷基、(C「C30)杂烷基、(C2-C30)烯基、(C2-C30)炔 基、芳基(Q-CJ烷基、被取代的(Ci-Cj烷基、被取代的(Q-CJ杂烷基、被取代的(c2-c3Q) 烯基、被取代的(C2_CJ炔基、或被取代的芳基沁-(3(|)烷基；(III). A3或A8或两者必须存在于所述化合物中；(IV).当 A2 是 Cys、D_Cys、hCys、D-hCys、Pen 或 D_Pen 时，则 A9 是 Cys、D_Cys、 hCys、D-hCys、Pen、或 D-Pen ；(V).当 A2 是 Asp 或 Glu 时，则 A9 是 Dab、Dap、Orn 或 Lys ;(VI) 当 A8 是 Ala 或 Gly 时，则 A1 不是 Nle ；(VII).当A1缺失时，则R2和R3不能都是H;或其可药用盐。在第一实施方案中的一个方面，本发明提供治疗哺乳动物受试者的胰岛素抵抗的 方法(伴随或不伴随体重减轻)，通过施用治疗有效量的前面通式I之黑皮质素受体配体的 亚组，其中A1 是 A6c、Arg、D_Arg、Cha、D_Cha、hCha、Chg、D_Chg、Gaba、lie、Leu、hLeu、Met、 3 -hMet、2-Nal、D-2-Nal、Nip、Nle、Oic、Phe、D_Phe、hPhe、hPro、Val 或缺失；A2 是 Asp、Cys、D_Cys、hCys、D-hCys、Glu、Pen 或 D-Pen ；A3 是 D-Abu、Aib、Ala、旦-Ala、D_Ala、D_Cha、Gaba、D_Glu、Gly、D_Ile、D_Leu、 D-Tle、D_Val 或缺失；A4 是 His 或 3-Pal ；A5 是 0-831、0-1-恥1、0-2-恥1、0-卩1^、0-11卬或0-伍01又『；A6 是 Arg 或 hArg ；AlBal、Bip、l-Nal、2-Nal、Trp、D_Trp ；A8 是 A6c、D-Ala、Aha、Ahx、Ala、3 -Ala、Apn、Gaba、Gly 或缺失；A9 是 Cys、D_Cys、hCys、D-hCys > Lys、Pen 或 D-Pen ；A10 是 Thr 或缺失；其中A3或A8的至少一个但不是两者被缺失，或其可药用盐。根据通式(I)的配体的前面组更优选的化合物(其用于治疗哺乳动物受试者的胰 岛素抵抗，伴随或不伴随体重减轻)是下述式的化合物Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-^ -Ala-Lys)-NH2 ；SEQ ID NO 1Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-A6c-Lys)-NH2 ;SEQ ID NO 1Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx_Cys)-NH2 ;SEQ ID NO 2D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-NH2 ;SEQ ID NO 3D-Ph e-c(Cys-His-D-Ph e—Arg—Trp-3—Ala—D—Cys)_Thr_NH2 ;SEQ ID NO 3D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)_Thr-NH2 ;SEQ ID NO 3Ac-Nle-c(Cys-His-D-Phe-Arg-Trp_Apn-Cys)-NH2 ;SEQ ID NO 2Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH2 ;SEQ ID NO 4Ac-A6c_c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)_NH2 ;SEQ ID NO 5Ac-D-2-Nal-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)_NH2 ;SEQ ID NO 6
Ac--Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO 6
Ac--Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO 6
Ac--Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 7
Ac--Nle-c(Cys-3-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ;SEQ ID NO 7
Ac--Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 7
Ac--Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 7
Ac--Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 7
Ac--Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 8
Ac--Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 8
Ac--Nle-c(D-Cys-0-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ;SEQ ID NO 8
Ac--Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 8
Ac--Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 8
Ac--Nle-c(D-Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 8
Ac--Nle-c(Cys-D-Ala-His-D-Ph e-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 9
Ac--Nle-c(Cys-^ -Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 9
Ac--Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 9
Ac--Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 9
Ac--Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 9
Ac--Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 10
Ac--Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 10
Ac--Nle-c(D-Cys-^ -Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 10
Ac--Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 10
Ac--Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 10
Ac--Oic-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO: 11
Ac—Chg—c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO: 11
Ac-_hCha_c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO: 11
Ac--D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO: 11
Ac-Nip-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO: 11
Ac--hPro-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO: 11
Ac-_hLeu_c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO: 11
Ac-_hCha_c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO: 11
Ac--Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO: 11
Ac--D-Phe-c(Asp-His-D-Ph e-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO 11
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO: 11
正丁酰基-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO: 12
Ac--hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO: 11
Ac--^ -hMet-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO 11
Ac--Gaba-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO: 11
Ac--Cha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2 ；SEQ ID NO: 13
Ac-hCha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2 ;SEQ ID NO: 13Ac-Leu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2 ;SEQ ID NO: 13Ac-hLeu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2 ;SEQ ID NO: 13Ac-Phe-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2 ;SEQ ID NO 13Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-D-Ala-Lys)-NH2 ;SEQ ID NO 14Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-^ -Ala-Lys)-NH2 ；SEQ ID NO 14Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Gaba-Lys)-NH2 ;SEQ ID NO: 14Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Aha-Lys)-NH2 ；SEQ ID NO: 14Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Apn-Lys)-NH2 ；SEQ ID NO 14Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-NH2 ;SEQ ID NO 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-NH2 ;SEQ ID NO 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-NH2 ;SEQ ID NO 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-3 -Ala-Cys)_NH2 ；SEQ ID NO 15Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-NH2 ;SEQ ID NO 15Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2 ;SEQ ID NO 16Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg_2-Nal-Cys)_NH2 ;SEQ ID NO 16Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-l-Nal-Cys)_NH2 ;SEQ ID NO 16正丁酰基-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)_NH2；SEQ IDNO 17IDNO 17Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)_NH2 ;SEQ ID NO 18Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-l-Nal-Cys)_NH2 ;SEQ ID NO 18Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Bal-Cys)_NH2 ;SEQ ID NO 18Ac-Nle-c(Cys-D-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 ;SEQ ID NO 61Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-D-Ala-Lys)-NH2 ;SEQ ID NO 19Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)_NH2 ;SEQ ID NO 20Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ;SEQ ID NO 21Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)_NH2 ;SEQ ID NO 22Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 ;SEQ ID NO 22D-Phe-c(Cys-His-D-Phe-hArg-Trp-^ -Ala-D-Cys)-Thr-NH2 ；SEQ ID NO 23D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-3-Ala-D-Cys)-Thr-NH2 ；SEQ IDNO 24D-Phe-c(Cys-His-D-Phe-Arg-Bip-^ -Ala-D-Cys)-Thr-NH2 ；SEQ ID NO 25D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-3-Ala-D-Cys)-Thr-NH2 ；SEQ IDNO 24D-Phe-c(Cys-His-D-Phe-hArg-Bip-^ -Ala-D-Cys)-Thr-NH2 ；SEQ ID NO 26D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-3-Ala-D-Cys)-Thr-NH2 ；SEQ IDNO 26Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2 ；SEQ ID NO 27Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH2 ;SEQ ID NO 28Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH2 ;SEQ ID NO 28Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH ;SEQ ID NO 29Ac-Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH2 ;SEQ ID NO 30
Ac-Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp_Cys)-NH2 ;SEQ ID NO 30Ac-Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp_Cys)-NH2 ;SEQ ID NO 30Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg_Trp-Cys)-NH2 ;SEQ ID NO 30Ac-Nle-c(Cys-D-Tle-His-D-Phe-Arg_Trp-Cys)-NH2 ;SEQ ID NO 30Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp_Cys)-NH2 ;SEQ ID NO 30
0147]Ac--Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-nh2seqIDno310148]Ac--Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-nh2seqIDno320149]Ac--Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-nh2seqIDno320150]Ac--Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-nh2seqIDno330151]Ac--Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-nh2seqIDno330152]Ac--Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-nh2seqIDno330153]Ac--Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-nh2seqIDno330154]Ac--Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-nh2seqIDno33Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 ;SEQ ID NO 33Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 ；SEQ ID NO 34Phe-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 ；SEQ ID NO 34Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba_Cys)-NH2 ;SEQ ID NO 35Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)_OH ;SEQ ID NO 36Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba_Cys)-NH2 ;SEQ ID NO 37Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH2 ;SEQ ID NO 38Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-^ -Ala-Lys)-NH2 ；SEQ ID NO 38Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba_Cys)-NH2 ;SEQ ID NO 39Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx_Cys)-NH2 ;SEQ ID NO 39Ac-hPh e-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2 ;SEQ ID NO 40Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)_NH2 ;SEQ ID NO 40Ac-Nle-c(Asp-His-D-Ph e-Arg-Trp-3-Ala-Lys)-OH ;SEQ ID NO 41Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)_OH ;SEQ ID NO 42D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-OH ;SEQ ID NO 43D-Phe-c(Cys-His-D-Phe-Arg-Trp-3 -Ala-D-Cys)-Thr-OH ；SEQ ID NO 43D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-OH ;SEQ ID NO 43Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-OH ;SEQ ID NO 42Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-OH ;SEQ ID NO 41Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH ;SEQ ID NO 44Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH ;SEQ ID NO 44Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH ;SEQ ID NO 29Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys) -OH ；SEQ ID NO 44Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH ;SEQ ID NO 44Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH ;SEQ ID NO 44Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys) -OH ；SEQ ID NO 44
33
Ac-hPhe-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH ;SEQ ID NO 44Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)_OH ;SEQ ID NO 45Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)_OH ;SEQ ID NO 45Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp_3 -Ala-Cys)_OH ；SEQ ID NO 45Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)_OH ;SEQ ID NO 45Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)_0H ;SEQ ID NO 46Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)_0H ;SEQ ID NO 46Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-l-Nal-Cys)_0H ;SEQ ID NO 46Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)_0H ;SEQ ID NO 46Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH ;SEQ ID NO 47Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH ;SEQ ID NO 29Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)_OH ;SEQ ID NO 48Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2 ;SEQ ID NO 49Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ;SEQ ID NO 50Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ;SEQ ID NO 50Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 ;SEQ ID NO 51Ac-D-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2 ;SEQ ID NO 52Ac-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2 ;SEQ ID NO52Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 ;SEQ ID NO 51Ac-D-Arg-c (Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2 ;SEQ ID NO 53Ac-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2 ;SEQ ID NO 53Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg_Trp-Cys)-NH2 ;SEQ ID NO 7D-Phe-c(Cys—His—D—(Et)Tyr-Arg-Trp-3 —Ala—D—Cys)_Thr_NH2 ；SEQ IDNO 24Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)_NH2 ;SEQ ID NO 27Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba_Pen)-NH2 ;SEQ ID NO 32Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba_Cys)-NH2 ;SEQ ID NO 34Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-^ -Ala-Lys)-NH2 ；SEQ ID NO 1Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx_Cys)-NH2 ;SEQ ID NO 2D-Phe-c(Cys-His-D-Phe-Arg-Trp-^ -Ala-D-Cys)-Thr-NH2 ；SEQ ID NO 3D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH2 ;SEQ ID NO 3Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2 ;SEQ ID NO 2Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH2 ;SEQ ID NO 4Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ;SEQ ID NO 6Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ;SEQ ID NO 6Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ;SEQ ID NO: 11Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ;SEQ ID NO: 11Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ;SEQ ID NO: 11Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ;SEQ ID NO: 11Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-^ -Ala-Cys)-NH2 ；SEQ ID NO 15
Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg_Trp-Cys)-NH2 ;SEQ ID NO 21Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)_NH2 ;SEQ ID NO 22D-Phe-c(Cys-His-D-Phe-hArg-Trp-^ -Ala-D-Cys)-Thr-NH2 ；SEQ ID NO 23D-Phe-c(Cys-His-D-Phe-Arg-Bip-^ -Ala-D-Cys)-Thr-NH2 ；SEQ ID NO 25D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-3 -Ala-D-Cys)_Thr_NH2 ；SEQ IDNO 24D-Phe-c(Cys-His-D-Phe-hArg-Bip-^ -Ala-D-Cys)-Thr-NH2 ；SEQ ID NO 26D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-3 -Ala-D-Cys)_Thr_NH2 ；SEQ IDNO 26Ac--Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-nh2；seqID NO28
Ac--Nle-c)(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-nh2；seqid no28
Ac--Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-oh ； seqid no29
Ac--Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH2；seqid no30
Ac--Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)-nh2；seqid no30
Ac--Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-nh2；seqid no30
Ac--Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-nh2；seqid no30
Ac--Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-nh2；seqid no30
Ac--Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-nh2；seqid no30
Ac--Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)_nh2seqid no 31
Ac--Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)_nh2seqid no 32
Ac--Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys) _nh2seqID NO 33
Ac--Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)_nh2seqID NO 33
Ac--Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)_nh2seqID NO 33
Ac--Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys) _nh2seqID NO 33
Ac--Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys) _nh2seqID NO 33Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba_Cys)-NH2 ;SEQ ID NO 33Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 ；SEQ ID NO 34Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba_Cys)-NH2 ;SEQ ID NO 35Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)_OH ;SEQ ID NO 36Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba_Cys)-NH2 ;SEQ ID NO 37Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp_Cys)-NH2 ;SEQ ID NO 16Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)_NH2 ;SEQ ID NO 16Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)_NH2 ;SEQ ID NO 20Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH2 ;SEQ ID NO 38Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-^ -Ala-Lys)-NH2 ；SEQ ID NO 38Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba_Cys)-NH2 ;SEQ ID NO 39Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx_Cys)-NH2 ;SEQ ID NO 39Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)_NH2 ;SEQ ID NO 40Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)_NH2 ；SEQ ID NO 40 或Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)_NH2 ;SEQ ID NO 49或其可药用盐。
在第二实施方案中，本发明提供治疗哺乳动物受试者中胰岛素抵抗的方法(伴随 或不伴随体重减轻)，通过施用治疗有效量的根据通式(II)的黑皮质素受体配体及其可药 用盐、水合物、溶剂化物或前药(见公开号为W02007/008704国际专利申请，此处整体引用 作为参考)(R2R3) -A1-。(A2-A3-A4-A5-A6-A7-A8-A9) _NH2(II)其中A1是Nle或缺失；A2 是 Cys 或 Asp ；A3 是 Glu 或 D-Ala ；A4 是 His;A5 是 D-Phe ；A6 是 Arg ；A7 是 Trp、2_Nal 或 Bal ；A8 是 Gly、Ala、D_Ala、3 -Ala、Gaba 或 Apn ；A9 是 Cys 或 Lys;R2和R3各自独立地选自H或(Q-Ce)酰基；条件是(I).当 R2 是(C「C6)酰基时，则 R3 是 H ；(II).当 A2 是 Cys 时，则 A9 是 Cys，或其可药用盐。前面组的化合物更优选的(其用于治疗哺乳动物受试者中胰岛素抵抗，伴随或不 伴随体重减轻)是下述式的化合物Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly_Cys)-NH2 ;SEQ ID NO 54Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D_Ala-Cys)-NH2 ;SEQ ID NO 54Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-^ -Ala-Cys)-NH2 ；SEQ ID NO 54Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba_Cys)-NH2 ;SEQ ID NO 54Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp_Apn-Cys)-NH2 ;SEQ ID NO 54Ac-c(Cys-Glu-His-D-Phe-Arg-Trp-Ala-Cys)-NH2 ；SEQ ID NO 55Ac-c(Cys-Glu-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2 ；SEQ ID NO 55Ac-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH2 ；SEQ ID NO 56Ac-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2 ；SEQ ID NO 56Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp_Ala-Cys)-NH2 ;SEQ ID NO 57Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-^ -Ala-Cys)-NH2 ；SEQ ID NO 57Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba_Cys)-NH2 ;SEQ ID NO :57 或Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal_Ala-Lys)-NH2 ;SEQ ID NO 58或其可药用盐。在第三实施方案中，本发明提供治疗哺乳动物受试者的胰岛素抵抗的方法(伴随 或不伴随体重减轻)，通过施用治疗有效量的根据式(III)的黑皮质素受体化合物、及其可药用盐、水合物、溶剂化物或前药(见公开号为W02007/008684国际专利申请，此处整体引 用作为参考)(R2R3) -B'-A-c (A2-A3-A4-A5-A6-A7-A8-A9) -A^-A'-A^-A^-B'-B'-R1(III)其中B1是含有5、6、7、8、9、10、11、12、13、14或15个氨基酸的肽部分，其中至少5个氨 基酸独立地选自L-Arg、D-Arg、L-hArg和D_hArg，或B1任选缺失；A1 是 Acc、HN- (CH2) m_C (0)、L_ 或 D_ 氨基酸或缺失；A2 是 Cys、D_Cys、hCys、D-hCys、Pen、D_Pen、Asp 或 Glu ；A3 是 Gly、Glu、Ala、3 -Ala、Gaba、Aib、D_ 氨基酸或缺失；八4是圯8、2-卩&1、3-卩&1、4-卩&1、1&2、2-111士、3-111土或(X1，X2，X3，X4，X5) Phe ；
A5 是 D-Phe、D-l-Nal、D_2_Nal、D-Trp、D_Bal、D_ (X1，X2，X3，X4，X5) Phe、D_ (Et) Tyr、 D-Dip、D-Bip 或D-Bpa ；A6 是 Arg、hArg、Dab、Dap、Lys、Orn 或 HN-CH((CH2)n_N(R4R5)) _C (0)；A7 是 Trp、l-Nal、2_Nal、Bal、Bip、Dip、Bpa、D-Trp> D-l-Nal> D_2_Nal、D_Bal、 D-Bip、D-Dip 或D-Bpa ；A8 是 Gly、D_Ala、Ace、Ala、3-Ala、Gaba、Apn、Ahx、Aha、HN_ (CH2) S_C (0)或缺失；A9 是 Cys、D_Cys、hCys、D-hCys> Pen、D_Pen、Dab、Dap、Orn 或 Lys ；A10 是 Acc、HN- (CH2) t_C (0)、Pro、hPro、3_Hyp、4_Hyp、Thr、L_ 或 D_ 氨基酸或缺失；A11 是 Pro、hPro、3-Hyp、4-Hyp 或缺失；A12 是 Lys、Dab、Dap、Arg、hArg 或缺失；A13 是 Asp、Glu 或缺失；B2是含有1、2、3、4或5个氨基酸的肽部分或缺失，B3是含有5、6、7、8、9、10、11、12、13、14或15个氨基酸的肽部分，其中至少5个氨 基酸独立地选自L-Arg、D-Arg、L-hArg和D_hArg或缺失；R1 是-0H 或-NH2;R2和R3各自在每种情况下独立地选自H、(CfCj烷基、(CfCj杂烷基、(Q-CJ 酰基 、(C2-C30)火布基、(C2_C30)块基、方基(C「C30)焼基、方基(C「C30) 酰基、被取代的(Ci-Cj 烷基、被取代的(Ci-Cj杂烷基、被取代的(Ci-Cj酰基、被取代的(C2-CJ烯基、被取代的 (c2-c30)炔基、被取代的芳基(Ci-Cj烷基、和被取代的芳基(Ci-Cj酰基；R4和R5各自在每种情况下独立地是H、(CrC40)烷基、(Q-C；。)杂烷基、(Q-C；。)酰 基、(C2-C40)火布基、(C2_C40)块基、方基(C「C40)焼基、方基(C「C40) 酰基、被取代的(c「c40) 烷基、被取代的(Ci-Cj杂烷基、被取代的(Q-Cd酰基、被取代的(c2-c4(l)烯基、被取代的 (c2-c40)炔基、被取代的芳基(crc4Q)烷基、被取代的芳基(crc4Q)酰基、(Ci-Cj烷基磺酰 基或-c(nh)-nh2 ；n在每种情况下独立地是1、2、3、4或5 ；m在每种情况下独立地是1、2、3、4、5、6或7;s在每种情况下独立地是1、2、3、4、5、6或7;t在每种情况下独立地是1、2、3、4、5、6或7;
37
^、^、^、义和^各自在每种情况下独立地是！^丄丨^广工、(U烷基、被取代 的(Cho)烷基、(c2_10)烯基、被取代的(c2_10)烯基、(c2_10)炔基、被取代的(c2_10)炔基、芳 基、被取代的芳基、OH、NH2、N02或CN ；条件是(I).当R4是(C「C40)酰基、芳基(C「C40)酰基、被取代的(C「C40)酰基、被取代的 芳基(c「c40)酰基、(C「C40)烷基磺酰基或-c (NH) -NH2时，则R5是H、(C「C40)烷基、(C「C40) 杂烷基、(C2-C40)烯基、(C2-C40)炔基、芳基(Q-C；。)烷基、被取代的(CrC4Q)烷基、被取代的 (crc40)杂烷基、被取代的(c2-c4Q)烯基、被取代的(c2-c4Q)炔基或被取代的芳基(Q-Cj烷 基；(II).当R2为和-(3(1)酰基、芳基和-(3(1)酰基、被取代的和-(3(1)酰基、或被取代 的芳基(c「c30)酰基时，则R3是H、(CrC30)烷基、(C「C30)杂烷基、(C2-C30)烯基、(C2-C30)炔 基、芳基(Q-CJ烷基、被取代的(Ci-Cj烷基、被取代的(Q-CJ杂烷基、被取代的(C2-C3Q) 烯基、被取代的(C2-CJ炔基、或被取代的芳基(Ci-Cj烷基；(III)B1和B2都不含有一种或更多种下述氨基酸序列Arg- (Lys) 2_ (Arg) 2_Gln_ (Arg) 3、Tyr-Ala-Arg-Lys-Ala- (Arg) 2-Gin-Ala- (Arg) 2、Tyr-Ala-Arg- (Ala) 2_ (Arg) 2_ (Ala) 2_ (Arg) 2、Tyr-Ala- (Arg) 9、Tyr- (Ala) 3_ (Arg) 7、Tyr-Ala-Arg-Ala-Pro- (Arg) 2_Ala_ (Arg) 3 或Tyr-Ala-Arg-Ala-Pro- (Arg) 2-Pro- (Arg) 2 ；(IV) B1或B2之一或两者必须存在于所述化合物中；(V)当 A2 是 Cys、D_Cys、hCys、D_hCys、Pen 或 D_Pen 时，则 A9 是 Cys、D_Cys、hCys、 D-hCys、Pen 或D-Pen ；(VI)当 A2 是 Asp 或 Glu 时，则 A9 是 Dab、Dap、Orn 或 Lys ；或其可药用盐。在第三实施方案中的一个方面，本发明涉及通式(III)的化合物治疗哺乳动物受 试者中胰岛素抵抗的应用(伴随或不伴随体重减轻)，其中B1 是 Arg-Ly s-Gln-Ly s-(Arg) 5、Arg-(Ly s) 2-Arg-Gln-(Arg) 4、 Arg-(Lys) 2-(Arg)3-Gln-(Arg)2、Arg-(Lys)2-(Arg)4_G 1 n-Arg、 Arg- (Lys) 2- (Arg) 5_Gln、Arg- (Lys) 2_Gln- (Arg) 5、Arg-Gln- (Lys) 2- (Arg) 5、 Arg-Gln-(Arg) 7、Arg-Gln-(Arg) 8、(Arg) 2_Gln_ (Arg) 6、(Arg) 2_Gln_ (Arg) 7、 (Arg)3-Gln-(Arg)5、(Arg) 3_Gln_ (Arg) 6、(Arg) 4_Gln_ (Arg) 4、(Arg) 4_Gln_ (Arg) 5、 (Arg)5、(Arg)5-Gln-(Arg)3、(Arg) 5_Gln_ (Arg) 4、(Arg)6、(Arg) 6_Gln_ (Arg) 3、(Arg)7、 (Arg) 7-Gln-(Arg)2, (Arg)8、(Arg) 8_Gln_Arg、(Arg)9、(Arg)9_Gln、(D_Arg)5、(D_Arg)6、 (D-Arg) 7、(D-Arg) 8、(D-Arg) 9、Gln-Arg- (Lys) 2- (Arg) 5、Gin- (Arg) 8、Gin- (Arg) 9、Tyr-Gly-Arg- (Lys) 2- (Arg) 2_Gln_ (Arg) 3、Tyr-Gly-Arg- (Lys) 2- (Arg) 2_Gln_ (Arg) 3_Doc ；或缺失；B2 是 3-Ala、3-Ala-Gly、3-Ala-Tyr、3-Ala-Tyr-Gly、(3_Ala)2、 -Ala)2_Gly、( 3 -Ala) 2_Tyr、( 3 -Ala)2-Tyr-Gly、Doc、Doc-Gly、Doc-Tyr、Doc-Tyr_Gly、
(Doc)2、(Doc)2_Gly、(Doc) 2_Tyr、Doc) 2_Tyr_Gly 或缺失；B3 是 Arg-Ly s-Gln-Lys-(Arg) 5、Arg-Ly s-(Arg) 3-Gln-(Arg) 3、Arg- (Lys) 2-Arg_Gln- (Arg) 4、Arg- (Lys) 2_Gln- (Arg) 5、Arg- (Lys) 2- (Arg) 2_Gln- (Arg) 3、 Arg - (Lys)2- (Arg) 3-G1n-(Arg)2、Arg - (Lys) 2-(Arg)4_Gln_Arg、 Arg- (Lys) 2- (Arg) 5_Gln、Arg-Gln- (Lys) 2- (Arg) 5、Arg-Gln- (Arg) 7、Arg-Gln- (Arg) 8、 (Arg) 2-Lys- (Arg) 2_Gln_ (Arg) 3、(Arg) 2_Gln_ (Arg) 6、(Arg) 2_Gln_ (Arg) ” (Arg)3-Gln-(Arg)5、(Arg) 3_Gln_ (Arg) 6、(Arg) 4_Gln_ (Arg) 4、(Arg) 4_Gln_ (Arg) 5、 (Arg)5、(Arg)5-Gln-(Arg)3、(Arg) 5_Gln_ (Arg) 4、(Arg)6、(Arg) 6_Gln_ (Arg) 3、(Arg)7、 (Arg) 7-Gln-(Arg)2, (Arg)8、(Arg) 8_Gln_Arg、(Arg)9、(Arg)9_Gln、(D_Arg)5、(D_Arg)6、 (D-Arg) 7、(D-Arg) 8、(D-Arg) 9、Gln-Arg- (Lys) 2- (Arg) 5、Gin- (Arg) 8、Gin- (Arg) 9 或缺失；A1 是 A6c、Cha、hCha、Chg、D_Chg、hChg、Gaba、hLeu、Met、3 -hMet、D_2_Nal、Nip、 Nle、Oic、Phe、D_Phe、hPhe、hPro 或缺失；A2是 CysA3 是 D_Abu、Aib、Ala、旦-Ala、D-Ala、D-Cha、Gaba、Glu、Gly、D-Ile、D-Leu、D_Met、 D-Nle、D-Phe、D_Tle、D_Trp、D-Tyr, D-Val 或缺失；A4 是 His;A5 是 D-BaLD-l-NaLDI-NaLD-PheiD-ft1，X2，X3，X4，X5) Phe、D_Trp 或 D_ (Et) Tyr ；A6 是 Arg 或 hArg ；八7是8&1、8士口、1-恥1、2-恥1、11印或0-11卬；A8 是 A5c、A6c、Aha、Ahx、Ala、3 -Ala、Apn、Gaba、Gly 或缺失；A9 是 Cys、D_Cys、hCys、D_hCys、Lys、Pen 或 D-Pen ；A1 是 Pro、Thr 或缺失；A11 是 Pro 或缺失；A12 是 arg、Lys 或缺失；A13 是 Asp 或缺失；R2和R3各自独立地是H或酰基；或其可药用盐。根据通式(III)化合物前面组的优选的配体(其用于治疗哺乳动物受试者之胰岛 素抵抗，伴随或不伴随体重减轻)是下述式的化合物Tyr-Gly-Arg- (Lys) 2_ (Arg) 2_Gln_ (Arg) 3-Nle_c (Asp-His-D-2-Nal-Arg-Trp-Lys )-NH2 ； (SEQ ID NO 60)Tyr-Gly-Arg- (Lys) 2_ (Arg) 2_Gln_ (Arg) 3-Doc-Nle_c (Asp-His-D-2-Nal-Arg-Trp -Lys)-NH2 ；(SEQ ID NO 61)Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-&-Ala-Tyr-Gly-Arg-(Lys) 2_ (Arg) 2_G1 n- (Arg) 3-NH2 ； (SEQ ID NO 62)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-&-Ala-Tyr-Gly-Arg-(Lys) 2_ (Arg) 2 -Gin-(Arg) 3-NH2 ； (SEQ ID NO 62)Nle-c (Asp-His-D-2-Nal-Arg-Trp-Lys) - (Doc) [Tyr-Gly-Arg- (Lys) 2_ (Arg) 2_G1 n- (Arg) 3-NH2 ； (SEQ ID NO 63)Ac-Nle-c (Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pro)2-Lys-Asp-Tyr-Gly-Arg- (Lys
39)2- (Arg) 2-Gln- (Arg) 3-NH2 ； (SEQ ID NO 64)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys) - (Pro) 2-Lys-Asp-Tyr-Gly-Arg-(Lys) 2-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 65)Ac-Nle-c (Asp-His-D-2-Nal-Arg-Trp-Lys) - ( & -Ala) 2-Tyr-Gly-Arg- (Lys) 2_ (Ar g) 2-Gln-(Arg) 3-NH2 ； (SEQ ID NO 66)Ac-Nle-c (Asp-His-D-2-Nal-Arg-Trp-Lys) - (Pro) 2-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys) 2-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 67)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Gly-Cys) - (Pro) 2-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys) 2-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 68)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala-Tyr-G ly-Arg- (Lys) 2- (Arg) 2-Gln- (Arg) 3-NH2 ； (SEQ ID NO 69)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys) 2-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 69)Ac-Nle-c (Asp-His-D-2-Nal-Arg-Trp-Lys) - (Doc) 2-Tyr-Gly-Arg- (Lys) 2_ (Arg) 2 -Gin-(Arg) 3-NH2 ； (SEQ ID NO 70)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala-Tyr -Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg) 3-NH2 ； (SEQ ID NO 71)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala- (Arg) 5 -Gin-(Arg) 3-NH2 ; (SEQ ID NO 72)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala-Gly-( Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO 73)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala-Tyr-G ly- (Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO 74)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala-Tyr-G ly-Arg-(Lys) 2-Arg-Gln-(Arg) 4-NH2 ； (SEQ ID NO 75) Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala-Tyr-G ly-Arg-(Lys) 2-Gln-(Arg) 5-NH2 ; (SEQ ID NO 76)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala-Tyr-G ly-Arg-Lys-Gln-Lys- (Arg) 5-NH2 ； (SEQ ID NO 77)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala-Tyr-G ly-Arg-(Lys) 2-(Arg) 4-Gln-Arg-NH2 ； (SEQ ID NO 78)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala-Tyr-A ib-Arg-(Lys) 2-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 79)Ac-c (Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2_Arg_Asp- & -Ala- (Ar g) g-Gln- (Arg) 3-NH2 ； (SEQ ID NO 80)Ac-c (Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala- (Ar g) g-Gln- (Arg) 3-NH2 ； (SEQ ID NO 80)Ac-c (Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala- (Ar g) 6-Gln-(Arg) 3-NH2 ； (SEQ ID NO 81)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys g) g-Gln- (Arg) 3-NH2 ； (SEQ ID NO 82)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys g) g-Gln- (Arg) 3-NH2 ； (SEQ ID NO 82)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys g) 6-Gln-(Arg) 3-NH2 ； (SEQ ID NO 81)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)--Gin-(Arg) 3-NH2 ； (SEQ ID NO 83)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)--Gin-(Arg) 3-NH2 ； (SEQ ID NO 84)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)--Gin-(Arg) 3-NH2 ； (SEQ ID NO 83)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-ly-Arg- (Lys) 2- (Arg) 3-Gln- (Arg) 2-NH2 ； (SEQ ID NO 85)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-ly-Arg-Gln- (Lys) 2- (Arg) 5-NH2 ； (SEQ ID NO 86)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-ly-Arg-(Lys) 2-(Arg) 5-Gln-NH2 ; (SEQ ID NO 87)Ac-c(Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys -Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg) 3-NH2 ； (SEQ ID NO 71)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-ly-Arg-(Lys)2-(Arg)2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 71)Ac-c(Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys g) 2-Lys-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 88)Ac-c(Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys -Lys-(Arg) 3-Gln-(Arg) 3-NH2 ; (SEQ ID NO 89)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys g) 2-Lys-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 88)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys -Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2 ; (SEQ ID NO 90)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys -(Arg) 2-Lys-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 91)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys -Arg-Lys-(Arg) 3-Gln-(Arg) 3-NH2 ; (SEQ ID NO 92)Ac-c(Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys g) 2-Lys-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 93)Ac-c(Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys -Lys-(Arg) 3-Gln-(Arg) 3-NH2 ; (SEQ ID NO 94)Ac-c(Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys
-(Pro) 2-Arg-Asp- & -Ala- (Ar
-(Pro) 2-Lys-Asp- & -Ala- (Ar
-(Pro) 2-Lys-Asp- & -Ala- (Ar
Pro) 2-Arg-Asp- & -Ala- (Arg),
Pro) 2-Arg-Asp- & -Ala- (Arg)；
)ro) 2-Lys-Asp-^ -Ala- (Arg),
Pro) 2-Lys-Asp-3 -Ala—Tyr—G
Pro) 2-Lys-Asp-3 -Ala—Tyr—G
Pro) 2-Lys-Asp-3 -Ala—Tyr—G
-(Pro) 2-Lys-Asp- 3 -Ala-Tyr
Pro) 2-Lys-Asp-3 -Ala—Tyr—G
-(Pro
-(Pro
-(Pro
-(Pro
-(Pro
-(Pro
-(Pro
-(Pro
-(Pro
「Lys-Asp- 3 -Ala- (Ar
「Lys-Asp-3 -Ala—Arg
「Lys-Asp- 3 -Ala- (Ar
「Lys—Asp— 3-Ala-Tyr
「Lys—Asp— 3-Ala-Gly
「Lys—Asp— 3-Ala-Gly
「Lys-Asp- 3 -Ala- (Ar
「Lys-Asp-3 -Ala—Arg
「Lys—Asp— 3-Ala-Tyr-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2 ; (SEQ ID NO 95)Ac-c(Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys)-(Pro -Gly-Arg-Lys- (Arg) 3-Gln- (Arg) 3-NH2 ； (SEQ ID NO 96)Ac-c(Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys)-(Pro -(Arg) 2-Lys-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 97)Ac-c(Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys)-(Pro -Arg-Lys-(Arg) 3-Gln-(Arg) 3-NH2 ; (SEQ ID NO 92)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro g) 2-Lys-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 98)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro -Lys-(Arg) 3-Gln-(Arg) 3-NH2 ; (SEQ ID NO 99)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro -Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2 ; (SEQ ID NO: 100)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro -Gly-Arg-Lys- (Arg) 3-Gln- (Arg) 3-NH2 ； (SEQ ID NO 101)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro -(Arg) 2-Lys-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO: 102)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro _ -Arg-Lys-(Arg) 3-Gln-(Arg) 3-NH2 ; (SEQ ID NO: 103)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala- (Arg) 2 -Lys-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO: 104)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2_Lys_Asp- 3 -Ala-Arg-L ys- (Arg) 3-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 105)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala-Tyr-G ly- (Arg) 2-Lys- (Arg) 2-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 100)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala-Tyr-G ly-Arg-Lys- (Arg) 3-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 101) Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala-Gly-( Arg) 2-Lys-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO: 102)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala-Gly-A rg-Lys-(Arg) 3-Gln-(Arg) 3-NH2 ; (SEQ ID NO: 103)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala-Tyr-G ly-Arg-(Lys)2-Arg-Gln-(Arg)4-NH2 ； (SEQ ID NO: 106)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala-Tyr-G ly-Arg- (Lys) 2-Gln- (Arg) 5-NH2 ； (SEQ ID NO: 107)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala-Tyr-G ly-Arg-Lys-Gln-Lys-(Arg)5-NH2 ； (SEQ ID NO : 108)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala-Tyr-G ly-Arg-Gln- (Lys) 2- (Arg) 5-NH2 ； (SEQ ID NO: 109)
2-Lys-Asp-3-Ala-Tyr 2-Lys-Asp-3-Ala-Gly 2-Lys-Asp-3-Ala-Gly 2-Lys-Asp-3 -Ala-(Ar 2-Lys-Asp-3-Ala—Arg 2-Lys-Asp-3-Ala-Tyr 2-Lys-Asp-3-Ala-Tyr 2-Lys-Asp-3-Ala-Gly 9-Lys-Asp-3-Ala-Gly
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-ly-Arg- (Lys) 2- (Arg) 3-Gln- (Arg) 2-NH2 ； (SEQ ID NO: 110)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-ly-Arg-(Lys) 2-(Arg) 4-Gln-Arg-NH2 ； (SEQ ID NO: 111)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-ly-Arg- (Lys) 2- (Arg) 5-Gln-NH2 ； (SEQ ID NO: 112)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)--Gin-(Arg) 3-NH2 ; (SEQ ID NO : 113)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)--Gin-(Arg) 3-NH2 ; (SEQ ID NO : 113)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-ly- (Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 114)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-ly- (Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 114)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)--Gin-(Arg) 4-NH2 ; (SEQ ID NO : 115)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)--Gin-(Arg) 4-NH2 ; (SEQ ID NO : 115)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-ly- (Arg) 5-Gln- (Arg) 4-NH2 ； (SE Q ID NO: 116)Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-ly- (Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO: 116)Ac-c(Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys g) g-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 117Ac-c(Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys g) g-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 117Ac-c (Cys-Glu-His-D-2-Nal g) g-Gln- (Arg) 4-NH2 ； (SEQ ID NO: 118Ac-c (Cys-Glu-His-D-2-Nal g) g-Gln- (Arg) 4-NH2 ； (SEQ ID NO: 118Ac-c (Cys-Glu-His-D-2-Nal g) 6-Gln-(Arg) 3-NH2 ; (SEQ ID NO: 119Ac-c (Cys-Glu-His-D-2-Nal g) 6-Gln-(Arg) 3-NH2 ; (SEQ ID NO: 119Ac-c(Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys -Gly- (Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 120)Ac-c(Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys -Gly- (Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 120)Ac-c(Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys
Pro) 2-Lys-Asp-3 -Ala—Tyr—G
Pro) 2-Lys-Asp-3 -Ala—Tyr—G
Pro) 2-Lys-Asp-3 -Ala—Tyr—G
)ro) 2-Lys-Asp- ^ -Ala- (Arg)；
Pro) 2-Arg-Asp- & -Ala- (Arg)；
Pro) 2-Lys-Asp-3 -Ala—Tyr—G
Pro) 2-Arg-Asp-3 -Ala—Tyr—G
)ro) 2-Lys-Asp-^ -Ala- (Arg)；
Pro) 2-Arg-Asp- & -Ala- (Arg)；
Pro) 2-Lys-Asp-3 -Ala—Tyr—G
Pro) 2-Arg-Asp-3 -Ala—Tyr—G
-Arg-1-Na1-Ala-Cys
-Arg-1-Na1-Ala-Cys
-Arg-1-Na1-Ala-Cys
-Arg-1-Na1-Ala-Cys
-(Pro
-(Pro
-(Pro
-(Pro
-(Pro
-(Pro
-(Pro
-(Pro
-(Pro
「Lys-Asp- 3 -Ala- (Ar
「Arg-Asp-& -Ala-(Ar
「Lys-Asp- 3 -Ala- (Ar
「Arg-Asp-& -Ala-(Ar
「Lys-Asp- 3 -Ala- (Ar
「Arg-Asp-& -Ala-(Ar
「Lys—Asp— 3-Ala-Tyr
「Arg-Asp-3-Ala-Tyr
「Lys—Asp— 3-Ala-Tyr
43-Gly- (Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO: 121)Ac-c(Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys)-(Pro -Gly- (Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO: 121)Ac-c(Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys)-(Pro -Gly- (Arg) 6-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 122)Ac-c(Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys)-(Pro -Gly- (Arg) 6-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 122)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro g) g-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 123)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro
g) g-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 123)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro g) 6-Gln-(Arg) 3-NH2 ; (SEQ ID NO: 124)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro g) 6-Gln-(Arg) 3-NH2 ; (SEQ ID NO: 124)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro g) g-Gln- (Arg) 4-NH2 ； (SEQ ID NO: 125)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro g) g-Gln- (Arg) 4-NH2 ； (SEQ ID NO: 125)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro -Gly- (Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 126)Ac-c(Cy s-G1u-H i s-D-2-Na1-Arg-2-Na1-A1a-Cy s)-(Pro -Gly- (Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 126)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro -Gly- (Arg) 6-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 127)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro -Gly- (Arg) 6-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 127)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro -Gly- (Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO: 128)Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro -Gly- (Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO: 128)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2_Lys_Asp- & -Ala- (Arg) -Gin-(Arg) 3-NH2 ; (SEQ ID NO : 129)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2_Arg_Asp- & -Ala- (Arg) 5 -Gin-(Arg) 3-NH2 ; (SEQ ID NO : 129)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2_Lys_Asp_ & -Ala- (Arg) 5 -Gin-(Arg) 4-NH2 ; (SEQ ID NO : 130)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2_Arg_Asp- & -Ala- (Arg) 5 -Gin-(Arg) 4-NH2 ; (SEQ ID NO : 130)
「Arg-Asp-3-Ala-Tyr
「Lys—Asp— 3-Ala-Tyr
「Arg-Asp-3-Ala-Tyr
「Lys-Asp- 3 -Ala- (Ar
「Arg-Asp-3 -Ala-(Ar
2-Lys-Asp-3 -Ala-(Ar 2-Arg-Asp-3 -Ala-(Ar 2-Lys-Asp-3-Ala-(Ar 2-Arg-Asp-3-Ala-(Ar 2-Lys-Asp-3-Ala-Tyr 2-Arg-Asp-3-Ala-Tyr 2-Lys-Asp-3-Ala-Tyr 2-Arg-Asp-3-Ala-Tyr 2-Lys-Asp-3-Ala-Tyr 2-Arg-Asp-3-Ala-Tyr
5
Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala- (Arg) 6 -Gln-(Arg) 3-NH2 ; (SEQ ID NO 131)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Arg_Asp- β -Ala- (Arg) 6 -Gln-(Arg) 3-NH2 ; (SEQ ID NO 131)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Gly-( Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 132)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-G Iy- (Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 133)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Arg-Asp- β -Ala-Tyr-G Iy- (Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 133) Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-G Iy- (Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO: 134)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Arg-Asp- β -Ala-Tyr-G Iy- (Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO: 134)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2_Lys_Asp- β -Ala-Tyr-G Iy-(Arg)6-Gln-(Arg)3-NH2 ; (SEQ ID NO: 135)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Arg-Asp- β -Ala-Tyr-G Iy-(Arg)6-Gln-(Arg)3-NH2 ; (SEQ ID NO: 135)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - (Doc) 2-Tyr-Gly-Arg- (Lys) 2_ (A rg) 2-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 136)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Tyr-Gly-Arg-(Lys) 2_A rg-Gln- (Arg) 4-NH2 ； (SEQ ID NO : 137)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-Arg-(Lys)2- (Arg )2-Gln-(Arg) 3-NH2 ; (SEQ ID NO: 136)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_N H2 ； (SEQ ID NO 138)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Gly- (Arg)「Gin- (Arg) 3 -NH2 ；(SEQ ID NO 138)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Gly- (Arg)「Gin- (Arg) 3 -NH2 ；(SEQ ID NO 138)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Tyr-Gly- (Arg) 5_Gln_ ( Arg) 3-NH2 ； (SEQ ID NO 139)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Gly- (Arg)「Gin- (Arg) 4 -NH2 ；(SEQ ID NO 140)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Tyr-Gly-(Arg) 2_Lys_ ( Arg) 2-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 141)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Tyr-Gly-Arg-Lys-(Arg )3-Gln-(Arg) 3-NH2 ; (SEQ ID NO: 142)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Gly- (Arg) 2_Lys_ (Arg) 2-Gln-(Arg) 3-NH2 ； (SEQ ID NO 141)Ac-Nle-c(Cys-D-Ala-His-D-Ph e-Arg-Trp-Cys)-β -Ala-Gly-Arg-Lys-(Arg)「G In- (Arg) 3-ΝΗ2 ； (SEQ ID NO 142)Ac-Nle-c (Cys-D-Ala-His-D-Ph e-Arg-Trp-Cys) - β -Ala- (Arg) 2_Lys_ (Arg) 2_G1 n-(Arg)3-NH2 ； (SEQ ID NO 143)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Arg-Lys-(Arg) 3_Gln-( Arg) 3-NH2 ； (SEQ ID NO 144)Ac-Nle-c(Cys-D-Ala-His-D-Ph e-Arg-Trp-Cys)-β -Ala-Tyr-Gly-Arg- (Lys) 2_A rg-Gln- (Arg) 4-NH2 ； (SEQ ID NO : 145)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-Arg-(Lys)2-(Arg )2-Gln-(Arg) 3-NH2 ； (SEQ ID NO 146) Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_N H2 ； (SEQ ID NO 148)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Gly- (Arg)「Gin- (Arg) 3 -NH2 ；(SEQ ID NO 147)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Tyr-Gly-(Arg) 5_Gln_( Arg) 3-NH2 ； (SEQ ID NO 147)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - ( β -Ala) 2_ (Arg) 5_Gln_ (Arg) 3_ NH2 ； (SEQ ID NO 148)Ac-Nle-c (Cys-D-Ala-His-D-Ph e-Arg-Trp-Cys) - ( β -Ala) 2-Gly- (Arg) 5_Gln_ (A rg) 3-NH2 ； (SEQ ID NO 149)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - ( β -Ala) 2-Tyr-Gly- (Arg) 5_Gln -(Arg)3-NH2 ； (SEQ ID NO 149)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) -Doc- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 151)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) -Doc-Gly- (Arg) 5_Gln_ (Arg) 3_N H2 ； (SEQ ID NO 150)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg) 5_Gln_ (Arg )3-NH2 ； (SEQ ID NO 150)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - (Doc) 2_ (Arg)「Gin- (Arg) 3_NH2 ； (SEQ ID NO 151) Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - (Doc) 2_Gly_ (Arg) 5_Gln_ (Arg) 3 -NH2 ；(SEQ ID NO 152)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - (Doc) 2-Tyr-Gly- (Arg) 5_Gln_ (A rg) 3-NH2 ； (SEQ ID NO 152)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 4_N H2 ； (SEQ ID NO 154)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Gly- (Arg)「Gin- (Arg) 4 -NH2 ；(SEQ ID NO 153)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Tyr-Gly-(Arg) 5_Gln_ ( Arg) 4-NH2 ； (SEQ ID NO 153)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β -Ala) 2_ (Arg) 5_Gln_(Arg) 4_ NH2 ； (SEQ ID NO 154)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - ( β -Ala) 2-Gly- (Arg) 5_Gln_ (Ar g) 4-NH2 ； (SEQ ID NO 155)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - ( β -Ala) 2-Tyr-Gly- (Arg) 5_Gln -(Arg)4-NH2 ； (SEQ ID NO 155)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) -Doc- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 157)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) -Doc-Gly- (Arg) 5_Gln_ (Arg) 4_N H2 ； (SEQ ID NO 156) Ac-Nle-c(Cys-D-Ala-His-D-Ph e-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg) 5_Gln_ (Arg )4-NH2 ；(SEQ ID NO 156)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - (Doc) 2_ (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 157)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - (Doc) 2_Gly_ (Arg) 5_Gln_ (Arg) 4 -NH2 ；(SEQ ID NO 158)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - (Doc) 2-Tyr-Gly- (Arg) 5_Gln_ (A rg) 4-NH2 ； (SEQ ID NO 158)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - β -Ala-Tyr-Gly-(Arg)5_Gln_(A rg) 3-NH2 ； (SEQ ID NO 159)Ac-Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 160)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys) - β -Ala-Tyr-Gly-(Arg) 5_Gln_ (Ar g) 3-NH2 ； (SEQ ID NO 161)Ac-Nle-c (Asp-His-D-Ph e-Arg-Trp-Ala-Lys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 162)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - β -Ala-Tyr-Gly- (Arg)「Gin- (Arg) 3_N H2 ； (SEQ ID NO 164)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - β -Ala-Gly- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 163)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-3-Ala-(Arg)5-Gln-(Arg)3-NH2 ； (SEQ ID NO 163)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - ( β -Ala) 2_Tyr_Gly- (Arg)「Gin- (Arg) 3-NH2 ； (SEQ ID NO 164)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - ( β -Ala) 2_Gly_ (Arg) 5_Gln_ (Arg) 3_N H2 ； (SEQ ID NO 165)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - ( β -Ala) 2_ (Arg) 5_Gln_ (Arg) 3_NH2 ；
47(SEQ ID NO 165)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) -Doc-Tyr-Gly- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 166)Ac-Nle-C(Asp-His-D-Phe-Arg-Trp-Lys)-DoC-Gly-(Arg)5-Gln-(Arg)3-NH2 ； (SEQ ID NO 166)Ac-Nle-C(Asp-His-D-Phe-Arg-Trp-Lys)-DoC-(Arg)5-Gln-(Arg)3-NH2 ； (SEQ ID NO 168)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - (Doc) 2_Tyr_Gly- (Arg)「Gin- (Arg) 3_N H2 ； (SEQ ID NO 167)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - (Doc) 2_Gly_ (Arg) 5-Gln- (Arg) 3_NH2 ； (SEQ ID NO 167)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - (Doc) 2_ (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 168) Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - β -Ala-Tyr-Gly- (Arg)「Gin- (Arg) 4_N H2 ； (SEQ ID NO 170)Ac-Nle-c (Asp-His-D-Ph e-Arg-Trp-Lys) - β -Ala-Gly- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 169)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - β -Ala- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 169)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - ( β -Ala) 2_Tyr_Gly- (Arg)「Gin- (Arg) 4-NH2 ；(SEQ ID NO 170)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - ( β -Ala) 2_Gly_ (Arg) 5_Gln_ (Arg) 4_N H2 ；(SEQ ID NO 171)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - ( β -Ala) 2_ (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 171)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) -Doc-Tyr-Gly- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 173)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) -Doc-Gly- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 172)Ac-Nle-C(Asp-His-D-Phe-Arg-Trp-Lys)-DoC-(Arg)5-Gln-(Arg)4-NH2 ； (SEQ ID NO 172)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - (Doc) 2_Tyr_Gly- (Arg)「Gin- (Arg) 4_N H2 ； (SEQ ID NO 173) Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - (Doc) 2_Gly_ (Arg) 5-Gln- (Arg) 4_NH2 ； (SEQ ID NO 174)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - (Doc) 2_ (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 174)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β -Ala-Lys)-β -Ala-Tyr-Gly-(Arg) 5_Gln_ (Arg)3-NH2 ； (SEQ ID NO 175)
48
Ac-Nle-c (Asp-His-D-Phe-Arg-Trp- β -Ala-Lys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_N H2 ； (SEQ ID NO 176)Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys) - β -Ala-Tyr-Gly-(Arg) 5_Gln_ (Ar g) 3-NH2 ； (SEQ ID NO 177)Ac-Nle-c (Cys-His-D-Phe-Arg-Trp-Ahx-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 178)D-Phe-c(Cys-Hi s-D-Phe-Arg-Trp-β -Ala-D-Cys)-Thr- β -Ala-Tyr-Gly-(Arg)5 -Gln-(Arg) 3-NH2 ; (SEQ ID NO : 179)D-Phe-c(Cys-His-D-Phe-Arg-Trp-β -Ala-D-Cys)-Thr- β -Ala- (Arg) 5_Gln_ (Ar g) 3-NH2 ； (SEQ ID NO 180)Ac-Nle-c(Cys-His-D-Ph e-Arg-Trp-Apn-Cys)-β -Ala-Tyr-Gly-(Arg)「Gin- (Ar g) 3-NH2 ； (SEQ ID NO 181)Ac-Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 182)Ac-Cha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys)- β -Ala-Tyr-Gly-(Arg) 5_Gln_ (A rg) 3-NH2 ； (SEQ ID NO 183)Ac-Cha-c (Asp-Hi s-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 184)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala-Tyr-Gly-(Arg)5_Gln_(A rg) 3-NH2 ； (SEQ ID NO 183)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 185)Ac-Chg-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala-Tyr-Gly-(Arg) 5_Gln_ (A rg) 3-NH2 ； (SEQ ID NO 186)Ac-Chg-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) -β -Ala-(Arg) 5_Gln_(Arg) 3_NH2 ； (SEQ ID NO 185)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala-Tyr-Gly-(Arg) 5_Gln_ ( Arg) 3-NH2 ； (SEQ ID NO 186)Ac-hCha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_N H2 ；(SEQ ID NO 188)Ac-hCha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - ( β -Ala) 2_Tyr_Gly- (Arg) 5_Gln -(Arg)3-NH2 ； (SEQ ID NO 187)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β -Ala) 2_ (Arg) 5_Gln_ (Arg) 3_ NH2 ；(SEQ ID NO 188)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly- (Arg) 5-Gln- (Arg )3-NH2 ； (SEQ ID NO 189)Ac-hCha-c (Asp-Hi s-D-Phe-Arg-Trp-Gaba-Lys) -Doc- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 190)Ac-hCha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - (Doc) 2_Tyr_Gly- (Arg) 5_Gln_ (Arg) 3-NH2 ； (SEQ ID NO 189)Ac-hCha-c (Asp-Hi s-D-Phe-Arg-Trp-Gaba-Lys) - (Doc) 2_ (Arg)「Gin- (Arg) 3_NH2 ； (SEQ ID NO 190)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala-Tyr-Gly-(Arg) 5-Gln-( Arg) 4-NH2 ； (SEQ ID NO 191)Ac-hCha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala- (Arg) 5_Gln_ (Arg) 4_N H2 ； (SEQ ID NO 192)Ac-bCha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - ( β -Ala) 2_Tyr_Gly- (Arg) 5_Gln -(Arg)4-NH2 ； (SEQ ID NO 191)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β -Ala) 2_ (Arg) 5_Gln_ (Arg) 4_ NH2 ；(SEQ ID NO 192)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly- (Arg) 5-Gln- (Arg )4-NH2 ； (SEQ ID NO 193)Ac-hCha-c (Asp-Hi s-D-Phe-Arg-Trp-Gaba-Lys) -Doc- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 194)Ac-hCha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - (Doc) 2-Tyr-Gly- (Arg) 5-Gln- (A rg) 4-NH2 ； (SEQ ID NO 193)Ac-hCha-c (Asp-Hi s-D-Phe-Arg-Trp-Gaba-Lys) - (Doc) 2_ (Arg)「Gin- (Arg) 4_NH2 ； (SEQ ID NO 194)Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β -Ala-Tyr-Gly-(Arg) 5_Gln_ (Arg)3-NH2 ； (SEQ ID NO 195)Ac-D-Chg-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_N H2 ；(SEQ ID NO 196)Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala-Tyr-Gly- (Arg) 5-Gln-( Arg) 3-NH2 ； (SEQ ID NO 197)Ac-hPhe-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala- (Arg) 5_Gln- (Arg) 3_N H2 ；(SEQ ID NO 198)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys) - β -Ala-Tyr-Gly- (Arg) 5_Gln_ ( Arg) 3-NH2 ； (SEQ ID NO 199)Ac-Nle-c (Cys-His-D-Phe-Arg-D-Trp-Apn-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_N H2 ；(SEQ ID NO 200)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys) - β -Ala-Tyr-Gly- (Arg) 5_Gln_ ( Arg) 3-NH2 ； (SEQ ID NO 199)Ac-Nle-c (Cys-His-D-Ph e-Arg-D-Trp-Ahx-Cys) - β -Ala- (Arg)「Gin- (Arg) 3_N H2 ；(SEQ ID NO 200)Ac-Nle-c(Cys-His-D-Ph e-Arg-D-Trp-β -Ala-Cys)- β -Ala-Tyr-Gly-(Arg) 5_G1 n-(Arg)3-NH2 ； (SEQ ID NO 201)Ac-Nle-c (Cys-His-D-Phe-Arg-D-Trp- β -Ala-Cys) - β -Ala- (Arg)「Gin- (Arg) 3_ NH2 ；(SEQ ID NO 202)
50
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) - β -Ala-Tyr-Gly- (Arg) 5_Gln_ ( Arg) 3-NH2 ； (SEQ ID NO 203)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) - β -Ala-Gly- (Arg)「Gin- (Arg) 3 -NH2 ；(SEQ ID NO 203)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) - β -Ala- (Arg) 5_Gln_ (Arg) 3_N H2 ； (SEQ ID NO 205)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) - ( β -Ala) 2-Tyr-Gly- (Arg) 5_Gln -(Arg)3-NH2 ； (SEQ ID NO 204)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) - ( β -Ala) 2-Gly- (Arg) 5_Gln_ (Ar g) 3-NH2 ； (SEQ ID NO 204)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) - ( β -Ala) 2_ (Arg) 5_Gln_ (Arg) 3_ NH2 ；(SEQ ID NO 205)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Tyr-Gly- (Arg) 5_Gln_ (Arg )3-NH2 ； (SEQ ID NO 207)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) -Doc-Gly- (Arg) 5_Gln_ (Arg) 3_N H2 ；(SEQ ID NO 206) Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) -Doc- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 206)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) - (Doc) 2_Tyr_Gly- (Arg) 5_Gln_ (A rg) 3-NH2 ； (SEQ ID NO 207)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) - (Doc) 2_Gly_ (Arg) 5_Gln_ (Arg) 3 -NH2 ； (SEQ ID NO 208)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) - (Doc) 2_ (Arg)「Gin- (Arg) 3_NH2 ； (SEQ ID NO 208)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β -Ala-D-Cys)-β -Ala-Tyr-Gly-(Arg)5 -Gln-(Arg) 3-NH2 ; (SEQ ID NO : 209)D-Phe-c(Cys-Hi s_D_(Et)Tyr-Arg-Trp- β -Ala-D-Cys)- β -Ala- (Arg) 5_Gln_ (Ar g) 3-NH2 ； (SEQ ID NO 210)D-Phe-c(Cys-His_D_(Et)Tyr-Arg-Trp- β -Ala-D-Cys)-β -Ala-Gly-(Arg) 5_Gln -(Arg)3-NH2 ； (SEQ ID NO 209)D-Phe-c(Cys-His_D_(Et)Tyr-Arg-Trp- β -Ala-D-Cys)- β -Ala- (Arg) 5_Gln_ (Ar g)4-NH2 ； (SEQ ID NO 211)D-Phe-c (Cys-Hi s_D_ (Et) Tyr-Arg-Trp- β -Ala-D-Cys) - ( β -Ala) 2_Tyr_Gly- (Ar g) s-Gln-(Arg) 3-NH2 ； (SEQ ID NO 212)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp- β -Ala-D-Cys)-(β -Ala) 2_ (Arg) 5_Gln_( Arg) 3-NH2 ； (SEQ ID NO : 213)D-Phe-c (Cys-His-D-(Et)Tyr-Arg-Trp-β -Ala-D-Cys)-la)[Gly-(Arg)5-Gl n-(Arg)3-NH2 ； (SEQ ID NO : 213)D-Phe-c (Cys-His-D- (Et) Tyr-Arg-Trp- β -Ala-D-Cys) - ( β -Ala) 2_ (Arg) 5_Gln_ (Arg)4-NH2 ； (SEQ ID NO 267)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp- β -Ala-D-Cys)-Doc-Tyr-Gly- (Arg) 5_G1 η-(Arg)3-NH2 ； (SEQ ID NO 214)D-Ph e-c (Cys-His-D- (Et) Tyr-Arg-Trp- β —Ala—D—Cys) -Doc- (Arg) 5_Gln_ (Arg) 3 -NH2 ； (SEQ ID NO 216)D-Ph e-c(Cys-His-D-(Et)Tyr-Arg-Trp- β —Ala—D—Cys)-Doc-Gly-(Arg) 5_Gln_ (A rg) 3-NH2 ； (SEQ ID NO 214)D-Phe-c (Cys-His-D- (Et) Tyr-Arg-Trp- β -Ala-D-Cys) -Doc- (Arg) 5_Gln_ (Arg) 4_ NH2 ； (SEQ ID NO : 217)D-Phe-c (Cys-His-D- (Et) Tyr-Arg-Trp- β -Ala-D-Cys) - (Doc) 2-Tyr-Gly- (Arg) 5_ Gln-(Arg) 3-NH2 ; (SEQ ID NO 215)D-Phe-c (Cys-His-D- (Et) Tyr-Arg-Trp- β -Ala-D-Cys) - (Doc) 2_ (Arg) 5_Gln_ (Arg )3-NH2 ； (SEQ ID NO 216)D-Phe-c (Cys-His-D- (Et) Tyr-Arg-Trp- β -Ala-D-Cys) - (Doc) 2-Gly- (Arg) 5_Gln_ (Arg)3-NH2 ； (SEQ ID NO : 215)D-Phe-c (Cys-His-D- (Et) Tyr-Arg-Trp- β -Ala-D-Cys) - (Doc) 2_ (Arg) 5_Gln_ (Arg )4-NH2 ； (SEQ ID NO : 217)D-Ph e-c(Cys-His-D-(Et)Tyr-hArg-Trp-β -Ala-D-Cys)-Thr-β -Ala-Tyr-Gly-(Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO 218)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β -Ala-D-Cys)-Thr-β -Ala-(Arg)5-Gl η-(Arg)3-NH2 ； (SEQ ID NO 219)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β -Ala-D-Cys)-Thr-(β -Ala)2-Tyr_Gl y-(Arg) 5-Gln-(Arg) 3-NH2 ； (SEQ ID NO 218)D-Phe-c (Cys-His-D-(Et)Tyr-hArg-Trp- β -Ala-D-Cys)-Thr-(β -Ala) 2_ (Arg) 5_ Gln-(Arg) 3-NH2 ; (SEQ ID NO 219)D-Phe-c (Cys-His-D- (Et)Tyr-hArg-Trp-β -Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg )5-Gln-(Arg) 3-NH2 ； (SEQ ID NO 221)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β -Ala-D-Cys)-Thr-Doc- (Arg) 5_Gln_ ( Arg) 3-NH2 ； (SEQ ID NO 220)D-Phe-c (Cys-His-D- (Et) Tyr-hArg-Trp- β -Ala-D-Cys) -Thr- (Doc) 2_Tyr_Gly-( Arg) 5-Gln-(Arg) 3-NH2 ； (SEQ ID NO 221)D-Phe-c (Cys-His-D- (Et)Tyr-hArg-Trp-β -Ala-D-Cys)-Thr- β -Ala-Tyr-Gly-( Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO : 222)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β -Ala-D-Cys)-Thr-β -Ala-(Arg)5-Gl n_(Arg)4-NH2 ； (SEQ ID NO 223)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β -Ala-D-Cys)-Thr-(β -Ala)2-Tyr-Gl y- (Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO : 222)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β -Ala-D-Cys)-Thr-(β -Ala)2_(Arg)5-Gln-(Arg) 4-NH2 ; (SEQ ID NO : 223)
D-Phe-c (Cys-His-D- (Et)Tyr-hArg-Trp-β -Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg )5-Gln-(Arg)4-NH2 ； (SEQ ID NO 224)D-Phe-c (Cys-His-D -(Et) Tyr-hArg-Trp - β - Ala-D-Cys)- Th r-Doc-(Arg) 5-Gln-(Arg) 4-NH2 ; (SEQ ID NO : 225)D-Phe-c (Cys-His-D-(Et) Tyr-hArg-Trp-β -Ala-D-Cys) -Thr-(Doc) 2_Tyr_Gly-( Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO : 224)D-Phe-c (Cys-His-D- (Et) Tyr-hArg-Trp- β —Ala—D—Cys) -Thr- (Doc) 2_ (Arg) 5_Gln -(Arg)4-NH2 ； (SEQ ID NO 225)D-Phe-c (Cys-Hi s_D_ (Et)Tyr-hArg-Bip- β -Ala-D-Cys)-Thr- β -Ala-Tyr-Gly-( Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO : 227)D-Phe-c (Cys-His_D_ (Et)Tyr-hArg-Bip-β -Ala-D-Cys)-Thr- β -Ala-Tyr-Gly-( Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO : 226)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β -Ala-D-Cys)-Thr-β -Ala-(Arg)5-Gl η-(Arg)3-NH2 ； (SEQ ID NO 228)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β -Ala-D-Cys)-Thr-(β -Ala)2-Tyr-Gl y- (Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO : 227)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β -Ala-D-Cys)-Thr-(β -Ala) 2_ (Arg) 5_ Gln-(Arg) 3-NH2 ; (SEQ ID NO : 228) D-Phe-c (Cys-His-D- (Et)Tyr-hArg-Bip-β -Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg )5-Gln-(Arg) 3-NH2 ； (SEQ ID NO 229)D-Phe-c (Cys-His-D- (Et)Tyr-hArg-Bip-β -Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg )5-Gln-(Arg)4-NH2 ； (SEQ ID NO 230)D-Phe-c(Cys-His_D_(Et)Tyr-hArg-Bip-β -Ala-D-Cys)-Thr-Doc- (Arg) 5_Gln_ ( Arg) 3-NH2 ； (SEQ ID NO 232)D-Phe-c (Cys-His-D- (Et) Tyr-hArg-Bip- β -Ala-D-Cys) -Thr- (Doc)2_Tyr_Gly-( Arg) 5-Gln-(Arg) 3-NH2 ； (SEQ ID NO 231)D-Ph e-c (Cys-His-D- (Et) Tyr-hArg-Bip- β -Ala-D-Cys) -Thr- (Doc) 2_ (Arg) 5_G1 n-(Arg)3-NH2 ； (SEQ ID NO 232)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys) - β -Ala-Tyr-Gly-(Arg) 5_G In-(Arg)3-NH2 ； (SEQ ID NO 233)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys) - β -Ala- (Arg)「Gin- (Arg) 3 -NH2 ； (SEQ ID NO 234)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys) - β -Ala-Tyr-Gly- (Arg)「Gin- (Arg) 3_ NH2 ；(SEQ ID NO 235)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 236)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys) - ( β -Ala) 2_Tyr_Gly- (Arg)「Gin- (Arg )3-NH2 ； (SEQ ID NO 235)Nle-C(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(^-Ala)2-(Arg)5-Gln-(Arg)3-NH2 ；(SEQ ID NO 236)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys) - β -Ala-Tyr-Gly- (Arg)「Gin- (Arg) 4_ NH2 ；(SEQ ID NO 237)Nle-c (Cys-His-D-Ph e-Arg-Trp-Apn-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 238)Nle-c (Cys-His-D-Ph e-Arg-Trp-Apn-Cys) - ( β -Ala) 2-Tyr-Gly- (Arg) 5_Gln_ (Ar g)4-NH2 ； (SEQ ID NO 237)Nle-c (Cys-His-D-Ph e-Arg-Trp-Apn-Cys) - ( β -Ala) 2_ (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 238)Nle-c (Cys-His-D-Ph e-Arg-Trp-Apn-Cys) -Doc-Tyr-Gly- (Arg)「Gin- (Arg) 3_N H2 ；(SEQ ID NO 239)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys) -Doc- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 240)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys) - (Doc) 2_Tyr_Gly- (Arg) 5_Gln_ (Arg) 3_ NH2 ；(SEQ ID NO 239)Nle-c (Cys—His—D—Ph e-Arg-Trp-Apn-Cys) - (Doc) 2_ (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 240)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys) -Doc-Tyr-Gly- (Arg) 5_Gln_ (Arg) 4_N H2 ；(SEQ ID NO 241)Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2 ； (SEQ ID NO 242)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys) - (Doc) 2_Tyr_Gly- (Arg) 5_Gln_ (Arg) 4_ NH2 ；(SEQ ID NO 241)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys) - (Doc) 2_ (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 242)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - β -Ala-Tyr-Gly-(Arg) 5_Gln_ ( Arg) 3-NH2 ； (SEQ ID NO 243)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_N H2 ； (SEQ ID NO 244)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - ( β -Ala) 2-Tyr-Gly- (Arg) 5_Gln -(Arg)3-NH2 ； (SEQ ID NO 243)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - ( β -Ala) 2_ (Arg) 5_Gln_ (Arg) 3_ NH2 ； (SEQ ID NO 244)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly- (Arg) 5_Gln_ (Arg )3-NH2 ； (SEQ ID NO 245)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) -Doc- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 246)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - (Doc) 2_Tyr_Gly- (Arg) 5_Gln_ (A rg) 3-NH2 ； (SEQ ID NO 245)
Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - (Doc) 2_ (Arg)「Gin- (Arg) 3_NH2 ； (SEQ ID NO 246)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - β -Ala-Tyr-Gly-(Arg) 5_Gln_ ( Arg)4-NH2 ； (SEQ ID NO 247)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 4_N H2 ； (SEQ ID NO 248)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - ( β -Ala) 2-Tyr-Gly- (Arg) 5_Gln -(Arg)4-NH2 ； (SEQ ID NO 247)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β -Ala) 2_ (Arg) 5_Gln_(Arg) 4-NH2 ；(SEQ ID NO 248)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly- (Arg) 5-Gln- (Arg )4-NH2 ； (SEQ ID NO 249)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) -Doc- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 250)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - (Doc) 2_Tyr_Gly- (Arg) 5_Gln_ (A rg)4-NH2 ； (SEQ ID NO 249)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - (Doc) 2_ (Arg)「Gin- (Arg) 4_NH2 ； (SEQ ID NO 250)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - β -Ala-Tyr-Gly-(Arg) 5_Gln_ ( Arg) 3-NH2 ； (SEQ ID NO 251) Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_N H2 ；(SEQ ID NO 252)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - ( β -Ala) 2-Tyr-Gly- (Arg) 5_Gln -(Arg)3-NH2 ； (SEQ ID NO 251)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - ( β -Ala) 2_ (Arg) 5_Gln_ (Arg)「 NH2 ；(SEQ ID NO 252)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly- (Arg) 5-Gln- (Arg )3-NH2 ； (SEQ ID NO 253)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) -Doc- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 254)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - (Doc) 2-Tyr-Gly- (Arg) 5_Gln_ (A rg) 3-NH2 ； (SEQ ID NO 253)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - (Doc) 2_ (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 254)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - β -Ala-Tyr-Gly-(Arg) 5_Gln_ ( Arg)4-NH2 ； (SEQ ID NO 255)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 4_N H2 ；(SEQ ID NO 256)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - ( β -Ala) 2-Tyr-Gly- (Arg) 5_Gln
55-(Arg)4-NH2 ； (SEQ ID NO 255) Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β -Ala) 2_ (Arg) 5_Gln_(Arg) 4_ NH2 ；(SEQ ID NO 256)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly- (Arg) 5_Gln_ (Arg )4-NH2 ； (SEQ ID NO 257)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) -Doc- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 258)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - (Doc) 2-Tyr-Gly- (Arg) 5_Gln_ (A rg)4-NH2 ； (SEQ ID NO 257)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - (Doc) 2_ (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 258)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - β -Ala-Tyr-Gly- (Arg) 5_Gln_ (Arg) 3 -NH2 ； (SEQ ID NO 259)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 260)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - ( β -Ala) 2_Tyr_Gly- (Arg) 5_Gln_ (Ar g) 3-NH2 ； (SEQ ID NO 259)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - ( β -Ala) 2_ (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 260)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - β -Ala-Tyr-Gly- (Arg) 5_Gln_ (Arg) 4 -NH2 ； (SEQ ID NO 261)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 262)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - ( β -Ala) 2_Tyr_Gly- (Arg) 5_Gln_ (Ar g)4-NH2 ； (SEQ ID NO 261)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - ( β -Ala) 2_ (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 262)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) -Doc-Tyr-Gly- (Arg) 5_Gln_ (Arg) 3_N H2 ； (SEQ ID NO 263)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) -Doc- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 264)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - (Doc) 2_Tyr_Gly- (Arg) 5_Gln_ (Arg) 3 -NH2 ；(SEQ ID NO 263)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - (Doc) 2_ (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 264)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) -Doc-Tyr-Gly- (Arg) 5_Gln_ (Arg) 4_N H2 ； (SEQ ID NO 265)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) -Doc- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 266)
56
Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - (Doc) 2_Tyr_Gly- (Arg) 5_Gln_ (Arg) 4 -NH2 ；(SEQ ID NO 265)或Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2 ； (SEQ ID NO 266)；或其可药用盐。在第四实施方案中，本发明提供治疗哺乳动物受试者中胰岛素抵抗的方法(伴随 或不伴随体重减轻)，通过施用治疗有效量的根据通式(IV)的黑皮质素受体化合物，及其 可药用盐、水合物、溶剂化物或前药，使用具有下述通式的化合物(通式(IV))Ac-c (Cys-Glu-Hi S-A1-Arg-A2-A3-CyS) - (Pro) [Lys-Asp-NH2(IV)其中A1是X-Phe或2_Nal的D-异构体，其中X是卤素；A2 是 Bal、I-Nal、2_Nal 或 Trp ；A3 是 Aib、Ala、β -Ala 或 Gly,或其可药用盐。发现用于治疗哺乳动物受试者中胰岛素抵抗(伴随或不伴随体重减轻)的前面通 式的优选的化合物包括下述化合物Ac-c (Cys-Glu-Hi s-D-4-Br-Phe-Arg-Trp-Gly-Cys) - (Pro) [Lys-Asp-NH2 ； (SEQ ID NO 268)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-NH2 ； (SEQ ID NO 269)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2-Lys-Asp-NH2 ； (SEQ ID NO 269)Ac-c (Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2-Lys-Asp-NH2 ； (SEQ ID NO 269)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-NH2 ； (SEQ ID NO 2690)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-β —Ala—Cys) - (Pro) 2-Lys_Asp-NH2 ； (SEQ ID NO 270)或Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Aib-Cys) - (Pro) 2-Lys-Asp-NH2 ； (SEQ ID NO 270)或其可药用盐。本发明另外提供治疗哺乳动物受试者中胰岛素抵抗的方法(伴随或不伴随体重 减轻)，通过施用治疗有效量的根据通式(V)、(VI)或(VII)的通过乙内酰脲部分修饰的黑 皮质素受体化合物，及其可药用盐、水合物、溶剂化物或前药。根据第五实施方案，本发明提供治疗哺乳动物受试者中胰岛素抵抗的方法(伴随 或不伴随体重减轻)，通过施用治疗有效量的根据下述通式(通式(V))的黑皮质素受体配 体，其可药用盐、水合物、溶剂化物和/或前药(见申请号为PCT/US08/06675国际专利申 请，此处整体引用作为参考)
(V)其中X 选自-CH2-S-S-CH2-、-C (CH3) 2-S-S_CH2-、-CH2-S-S-C (CH3) 2_、-C (CH3) 2-S_S_C (CH3) 2_、-(CH2)2-S-S-CH2-, -CH2-S-S-(CH2) 2_、- (CH2) 2_S_S-(CH2) 2_、-C(CH3)2-S-S-(CH2)-2_、- (CH2) 2-S-S-C (CH3) 2_、- (CH2) t-C (0) -NR8- (CH2) r-和 _ (CH2) r_NR8_C (0) _ (CH2) t-；R1和R2各自独立地是H、(C1-C10)烷基或被取代的(C1-Cltl)烷基；R3 是-OH 或-NH2;R4和R5各自独立地是H、(C1-C10)烷基或被取代的(C1-Cltl)烷基；
R6 R7X1 是O .A1 是 His、2-Pal、3-Pal、4-Pal、(X1，X2，X3，X4，X5)Phe、Taz、2_Thi、3_Thi 或缺失；A2 是 D-Bal、D-I-Nal、D-2_Nal、D-Phe 或 D-G1，X2，X3，X4X5) Phe ；A3 是 Arg、hArg、Dab、Dap、Lys 或 Orn ；A4 是 Bal、l-Nal、2_Nal、(X1, X2，X3，X4，X5) Phe 或 Trp ；R6和R7各自在其每种情况下独立地是H、(C1-C10)烷基、(C1-C10)杂烷基、芳基 (C1-C5)烷基、被取代的(C1-Cltl)烷基、被取代的(C1-Cltl)杂烷基或被取代的芳基(C1-C5)烷 基，条件是R6和R7可以结合在一起形成环；R8是H、(C1-C10)烷基或被取代的(C1-Cltl)烷基；r在其每种情况下独立地是1、2、3、4或5 ；t在其每种情况下独立地是1或2。优选地，发现用于治疗哺乳动物受试者中胰岛素抵抗(伴随或不伴随体重减轻) 的根据前面通式的化合物包括化合物其中X1选自
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权利要求
一种治疗有其需要的受试者中胰岛素抵抗的方法，包括外周施用有效量的黑皮质素受体4激动剂以治疗所述有其需要的受试者之所述胰岛素抵抗。
2.根据权利要求1的方法，其中用于治疗胰岛素抵抗的所述的黑皮质素受体4激动剂 选自Ac-Nle-c(Asp-His-D-Phe-Arg-Trp β -Ala-Lys)-NH2 ；SEQ ID NO 1 Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-A6c-Lys)-NH2 ；SEQ ID NO 1 Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH2 ；SEQ ID NO 2 D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-NH2 ；SEQ ID NO 3 D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-NH2 ;SEQ ID NO 3 D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH2 ；SEQ ID NO 3 Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2 ；SEQ ID NO 2 Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH2 ;SEQ ID NO 4 Ac-A6c-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ;SEQ ID NO 5 Ac-D-2-Nal-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ;SEQ ID NO 6 Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ;SEQ ID NO 6 Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ;SEQ ID NO 6 Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 7 Ac-Nle-c(Cys-β -Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 7 Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 7 Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 7 Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 7 Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 8 Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 8 Ac-Nle-c(D-Cys-β -Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 8 Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 8 Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 8 Ac-Nle-c(D-Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 8 Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 9 Ac-Nle-c(Cys-β -Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 9 Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 9 Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 9 Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 9 Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 10 Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 10 Ac-Nle-c(D-Cys-β -Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 10 Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 10 Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2 ；SEQ ID NO 10 Ac-Oic-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ;SEQ ID NO 11 Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO 11Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO 11 Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO 11 Ac-Nip-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO 11 Ac-hPro-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO 11 Ac-hLeu-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO 11 Ac-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO 11 Ac-D-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO 11 Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO 11 正丁酰基-Cha-C(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ； SEQ ID NO: 12 Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO 11 Ac-β -hMet-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO 11 Ac-Gaba-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO 11 Ac-Cha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2 ；SEQ ID NO 13 Ac-hCha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2 ;SEQ ID NO 13 Ac-Leu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2 ；SEQ ID NO 13 Ac-hLeu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2 ;SEQ ID NO 13 Ac-Phe-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2 ；SEQ ID NO 13 Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-D-Ala-Lys)-NH2 ；SEQ ID NO 14 Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-β -Ala-Lys)-NH2 ；SEQ ID NO 14 Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Gaba-Lys)-NH2 ;SEQ ID NO 14 Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Aha-Lys)-NH2 ;SEQ ID NO 14 Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Apn-Lys)-NH2 ;SEQ ID NO 14 Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-NH2 ；SEQ ID NO 15 Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-NH2 ；SEQ ID NO 15 Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-NH2 ；SEQ ID NO 15 Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β -Ala-Cys)-NH2 ；SEQ ID NO 15 Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-NH2 ；SEQ ID NO 15 Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2 ；SEQ ID NO 16 Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-NH2 ；SEQ ID NO 16 Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-l-Nal-Cys)-NH2 ；SEQ ID NO 16 正丁酰基-Nle-c (Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys) -NH2 ；SEQ IDNO 17 正丁酰基-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ;SEQ ID NO: 17 Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2 ；SEQ ID NO 18 Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-I-Nal-Cys)-NH2 ；SEQ ID NO 18 Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Bal-Cys)-NH2 ；SEQ ID NO 18 Ac-Nle-c(Cys-D-Glu-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 59 Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-D-Ala-Lys)-NH2 ；SEQ ID NO 19 Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-NH2 ；SEQ ID NO 20 Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 213Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 ；SEQ ID NO 22 Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 ；SEQ ID NO 22 D-Phe-c(Cys-His-D-Phe-hArg-Trp-β-Ala-D-Cys)-Thr-NH2 ；SEQ ID NO 23 D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp- β -Ala-D-Cys)-Thr-NH2 ；SEQ IDNO 24 D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr-NH2 ;SEQ ID NO 25 D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β -Ala-D-Cys)-Thr-NH2 ；SEQ IDNO 24 D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr-NH2 ；SEQ ID NO 26 D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β -Ala-D-Cys)-Thr-NH2 ；SEQ IDNO 26 Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2 ；SEQ ID NO 27Ac--Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH2；SEQIDNO28Ac--Nle-c^ (Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH2；SEQIDNO28Ac--Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH ； SEQIDNO29Ac--Nle-c(Cys-D-Abu-Hi s-D-Phe-Arg-Trp-Cys)-NH2；SEQIDNO30Ac--Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)-NH2；SEQIDNO30Ac--Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH2；SEQIDNO30Ac--Nle-c(Cys-D-Leu-Hi s-D-Phe-Arg-Trp-Cys)-NH2；SEQIDNO30Ac--Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH2；SEQIDNO30Ac--Nle-c(Cys-D-Cha-Hi s-D-Phe-Arg-Trp-Cys)-NH2；SEQIDNO30Ac--Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys) _NH2SEQIDNO 31Ac--Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)_NH2SEQIDNO 32Ac--Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)_NH2SEQIDNO 32Ac--Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys) _NH2SEQIDNO 33Ac--Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys) _NH2SEQIDNO 33Ac--Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)_NH2SEQIDNO 33Ac--Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys) _NH2SEQIDNO 33Ac--Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)_NH2SEQIDNO 33Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 ;SEQ ID NO 33 Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 ；SEQ ID NO 34 Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 ；SEQ ID NO 34 Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2 ；SEQ ID NO 35 Ac-Nle-c (Cys-D-Ala-His-D-Ph e-Arg-Trp-Cys)-OH ；SEQ ID NO 36 Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)-NH2 ；SEQ ID NO 37 Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH2 ；SEQ ID NO 38 Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-β -Ala-Lys)-NH2 ；SEQ ID NO 38 Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH2 ；SEQ ID NO 39 Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH2 ；SEQ ID NO 39 Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2 ;SEQ ID NO 40 Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2 ；SEQ ID NO 40 Ac-Nle-c (Asp-His-D-Phe-Arg-Trp- β -Ala-Lys)-OH ；SEQ ID NO 41Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-OH ；SEQ ID NO 42 D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-OH ；SEQ ID NO 43 D-Phe-c (Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-OH ；SEQ ID NO 43 D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-OH ；SEQ ID NO 43 Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-OH ；SEQ ID NO 42 Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys) -OH ；SEQ ID NO 41 Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH ；SEQ ID NO 44 Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) -OH ；SEQ ID NO 44 Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH ；SEQ ID NO 44 Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH ；SEQ ID NO 44 Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH ；SEQ ID NO 44 Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH ；SEQ ID NO 44 Ac-hPhe-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH ；SEQ ID NO 44 Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-OH ；SEQ ID NO 45 Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys) -OH ；SEQ ID NO 45 Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp- β -Ala-Cys)-OH ；SEQ ID NO 45 Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-OH ；SEQ ID NO 45 Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-OH ；SEQ ID NO 46 Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-OH ；SEQ ID NO 46 Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-l-Nal-Cys)-OH ；SEQ ID NO 46 Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-OH ；SEQ ID NO 46 Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH ；SEQ ID NO 47 Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen) -OH ；SEQ ID NO 48 Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2 ；SEQ ID NO 49 Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 50 Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ；SEQ ID NO 50 Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 ；SEQ ID NO 51 Ac-D-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2 ；SEQ ID NO 52 Ac-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2 ；SEQ ID NO 52 Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 ；SEQ ID NO 51 Ac-D-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2 ；SEQ ID NO 53 Ac-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2 ；SEQ ID NO 53 Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2 ；SEQ ID NO 35 Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-NH2 ；SEQ ID NO 54 Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Ala-Cys)-NH2 ；SEQ ID NO 54 Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- β -Ala-Cys)-NH2 ；SEQ ID NO 54 Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2 ；SEQ ID NO 54 Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Apn-Cys)-NH2 ；SEQ ID NO 54 Ac-c(Cys-Glu-His-D-Phe-Arg-Trp-Ala-Cys)-NH2 ；SEQ ID NO 55Ac-c(Cys-Glu-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2 ；SEQ ID NO 55 Ac-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH2 ；SEQ ID NO 56 Ac-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2 ；SEQ ID NO 56 Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH2 ；SEQ ID NO 57 Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp- β -Ala-Cys)-NH2 ；SEQ ID NO 57 Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Ala-Lys)-NH2 ；SEQ ID NO 58 Tyr-Gly-Arg- (Lys) 2_ (Arg) 2_Gln_ (Arg) 3_Nle_c (Asp-His-D-2-Nal-Arg-Trp-Lys) -N H2 ； (SEQ ID NO 60)Tyr-Gly-Arg- (Lys) 2- (Arg) 2-Gln_ (Arg) 3-Doc-Nle-c (Asp-His-D-2-Nal-Arg-Trp-Lys )-NH2 ； (SEQ ID NO 61)Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β -Ala-Tyr-Gly-Arg-(Lys) 2- (Arg) 2-Gln-(A rg) 3-NH2 ； (SEQ ID NO 62)Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)- β -A1a-Tyr-G1y-Arg-(Lys) 2- (Arg) 2-Gln -(Arg)3-NH2 ； (SEQ ID NO 62)Nle-c (Asp-His-D-2-Nal-Arg-Trp-Lys) - (Doc) 2-Tyr-GIy-Arg- (Lys) 2- (Arg) 2-Gln- (A rg) 3-NH2 ； (SEQ ID NO 63)Ac-Nle-c (Asp-His-D-2-Nal-Arg-Trp-Lys) - (Pro) 2-Lys-Asp-Tyr-Gly-Arg- (Lys) 2- (A rg) 2-Gln- (Arg) 3-NH2 ； (SEQ ID NO 64)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Trp-Gly-Cys) - (Pro) 2_Lys-Asp-Tyr-Gly-Arg- (Lys )2- (Arg) 2-Gln- (Arg) 3-NH2 ； (SEQ ID NO 65)Ac-Nle-c (Asp-His-D-2-Nal-Arg-Trp-Lys) - ( β -Ala) 2-Tyr-Gly-Arg- (Lys) 2_ (Arg) 2_ Gln-(Arg)3-NH2 ； (SEQ ID NO 66)Ac-Nle-c (Asp-His-D-2-Nal-Arg-Trp-Lys) - (Pro) 2-Lys-Asp-Doc-Tyr-Gly-Arg- (Lys )2- (Arg) 2-Gln- (Arg) 3-NH2 ； (SEQ ID NO 67)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Trp-Gly-Cys) - (Pro) 2-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys) 2-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 68)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-Gly-A rg-(Lys) 2-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 69)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2-Lys-Asp-Doc-Tyr-Gly-Arg-(Lys) 2-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 69)Ac-Nle-c (Asp-His-D-2-Nal-Arg-Trp-Lys) - (Doc) 2-Tyr-Gly-Arg- (Lys) 2- (Arg) 2-Gln -(Arg)3-NH2 ； (SEQ ID NO 70)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-Gly -Arg-(Lys)2-(Arg)2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 71)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala- (Arg) 5_Gln -(Arg)3-NH2 ； (SEQ ID NO 72)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Gly- (Arg) 5 -Gln-(Arg) 3-NH2 ; (SEQ ID NO 73)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-Gly-(Arg) 5-Gln- (Arg) 3"NH2 ； (SEQ ID NO 74)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2_Lys_Asp- β -Ala-Tyr-Gly-A rg- (Lys) 2-Arg-Gln- (Arg) 4-NH2 ； (SEQ ID NO 75)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2_Lys_Asp- β -Ala-Tyr-Gly-A rg- (Lys) 2-Gln- (Arg) 5-NH2 ； (SEQ ID NO 76)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2_Lys_Asp- β -Ala-Tyr-Gly-A rg-Lys-Gln-Lys- (Arg) 5-NH2 ； (SEQ ID NO 77)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2_Lys_Asp- β -Ala-Tyr-Gly-A rg- (Lys) 2- (Arg) 4-Gln-Arg-NH2 ； (SEQ ID NO 78)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2_Lys_Asp- β -Ala-Tyr-Aib-A rg-(Lys) 2-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 79)Ac-c (Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2_Arg_Asp- β -Ala- (Arg) 5_G In-(Arg)3-NH2 ； (SEQ ID NO 80)Ac-c (Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2_Lys_Asp- β -Ala- (Arg) 5_G In-(Arg)3-NH2 ； (SEQ ID NO 80)Ac-c (Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2_Lys_Asp- β -Ala- (Arg) 6_G In-(Arg)3-NH2 ； (SEQ ID NO 81)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2_Arg_Asp- β -Ala- (Arg) 5_G In-(Arg)3-NH2 ； (SEQ ID NO 82)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2_Lys_Asp- β -Ala- (Arg) 5_G In-(Arg)3-NH2 ； (SEQ ID NO 82)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2_Lys_Asp- β -Ala- (Arg) 6_G In-(Arg)3-NH2 ； (SEQ ID NO 81)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Arg-Asp- β -Ala- (Arg) 6_Gln -(Arg)3-NH2 ； (SEQ ID NO 83)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Arg-Asp- β -Ala- (Arg) 5_Gln -(Arg)3-NH2 ； (SEQ ID NO 84)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2_Lys_Asp- β -Ala- (Arg) 6_Gln -(Arg)3-NH2 ； (SEQ ID NO 83)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2_Lys_Asp- β -Ala-Tyr-Gly-A rg-(Lys) 2-(Arg) 3-Gln-(Arg) 2-NH2 ; (SEQ ID NO 85)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2_Lys_Asp- β -Ala-Tyr-Gly-A rg-Gln- (Lys) 2- (Arg) 5-NH2 ； (SEQ ID NO 86)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Trp-A 1 a-Cys) - (Pro) 2_Lys_Asp- β -Ala-Tyr-Gly-A rg- (Lys) 2- (Arg) 5-Gln-NH2 ； (SEQ ID NO 87)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2_Lys_Asp- β -Ala-Tyr-Gly -Arg-(Lys)2-(Arg)2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 71)Ac-c (Cys-G1 u-His-D-2-Na 1 -Arg-Ba 1 -A 1 a-Cys) - (Pro) 2_Lys_Asp- β -Ala-Tyr-Gly-A rg-(Lys) 2-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 71)7Ac-c (Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala- (Arg) 2~L ys- (Arg) 2-Gln- (Arg) 3-NH2 ； (SEQ ID NO 88)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Arg-Lys -(Arg) 3-Gln- (Arg) 3-NH2 ； (SEQ ID NO 89)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala- (Arg) 2~L ys- (Arg) 2-Gln- (Arg) 3-NH2 ； (SEQ ID NO 88)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-Gly -(Arg) 2-Lys-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 90)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Gly- (Ar g) 2-Lys-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 91)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Gly-Arg -Lys-(Arg) 3-Gln-(Arg) 3-NH2 ; (SEQ ID NO 92)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-Gly -(Arg) 2-Lys-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 95)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-I-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-Gly -Arg-Lys-(Arg) 3-Gln-(Arg) 3-NH2 ; (SEQ ID NO 96)Ac-c (Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Gly- (Ar g) 2-Lys-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO 97)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-I-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Gly-Arg -Lys-(Arg) 3-Gln-(Arg) 3-NH2 ; (SEQ ID NO 92)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala- (Arg) 2~L ys- (Arg) 2-Gln- (Arg) 3-NH2 ； (SEQ ID NO 98)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Arg-Lys -(Arg) 3-Gln- (Arg) 3-NH2 ； (SEQ ID NO 99)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-Gly -Arg-Lys-(Arg) 3-Gln-(Arg) 3-NH2 ; (SEQ ID NO: 101)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala- (Arg) 2-Lys -(Arg) 2-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 104)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Arg-Lys-( Arg) 3-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 105)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-Gly-( Arg) 2-Lys-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO: 100)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-Gly-A rg-Lys-(Arg) 3-Gln-(Arg) 3-NH2 ; (SEQ ID NO: 101)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Gly- (Arg) 2 -Lys-(Arg) 2-Gln-(Arg) 3-NH2 ; (SEQ ID NO: 102)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Gly-Arg-L ys- (Arg) 3-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 103)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala- (Arg)「Gin-(Arg) 3-NH2 ； (SEQ ID NO 113)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2-Arg-Asp- β -Ala- (Arg)「Gin -(Arg) 3-NH2 ； (SEQ ID NO : 113)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-Gly-( Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 114)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2-Arg-Asp- β -Ala-Tyr-Gly-( Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 114)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala- (Arg)「Gin -(Arg) 4-NH2 ； (SEQ ID NO : 115)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2-Arg-Asp- β -Ala- (Arg)「Gin -(Arg) 4-NH2 ； (SEQ ID NO : 115)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-Gly-( Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO: 116)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Trp-Ala-Cys) - (Pro) 2-Arg-Asp- β -Ala-Tyr-Gly-( Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO: 116)Ac-c (Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala- (Arg) 5_G In- (Arg) 4-NH2 ； (SEQ ID NO : 118)Ac-c (Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2-Arg_Asp- β -Ala- (Arg) 5_G In- (Arg) 4-NH2 ； (SEQ ID NO : 118)Ac-c (Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2-Arg_Asp- β -Ala- (Arg) 6_G In- (Arg) 3-NH2 ； (SEQ ID NO : 119)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-I-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-Gly -(Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 120)Ac-c (Cys-Glu-His-D-2-Nal-Arg-I-Nal-Ala-Cys) - (Pro) 2-Arg-Asp- β -Ala-Tyr-Gly -(Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 120)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-Gly -(Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO: 121)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2-Arg-Asp- β -Ala-Tyr-Gly -(Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO: 121)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-Gly -(Arg) 6-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 122)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2-Arg-Asp- β -Ala-Tyr-Gly -(Arg) 6-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 122)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2-Arg_Asp- β -Ala- (Arg) 6_G In- (Arg) 3-NH2 ； (SEQ ID NO : 124)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala- (Arg) 5_G In- (Arg) 4-NH2 ； (SEQ ID NO : 125)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2-Arg_Asp- β -Ala- (Arg) 5_G In- (Arg) 4-NH2 ； (SEQ ID NO : 125)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-Gly -(Arg) 5-Gln- (Arg) 3"ΝΗ2 ； (SEQ ID NO: 126)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2-Arg-Asp- β -Ala-Tyr-Gly -(Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 126)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-Gly -(Arg) 6-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 127)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2-Arg-Asp- β -Ala-Tyr-Gly -(Arg) 6-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 127)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-Gly -(Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO: 128)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2-Arg-Asp- β -Ala-Tyr-Gly -(Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO: 128)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala- (Arg) 5_Gln -(Arg)4-NH2 ； (SEQ ID NO 130)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Arg-Asp- β -Ala- (Arg) 5_Gln -(Arg)4-NH2 ； (SEQ ID NO 130)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Arg-Asp- β -Ala-Tyr-Gly-( Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 133)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-Gly-( Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO: 134)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Arg-Asp- β -Ala-Tyr-Gly-( Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO: 134)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Lys-Asp- β -Ala-Tyr-Gly-( Arg) 6-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 135)Ac-c (Cys-Glu-Hi s-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Arg-Asp- β -Ala-Tyr-Gly-( Arg) 6-Gln- (Arg) 3-NH2 ； (SEQ ID NO: 135)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - (Doc) 2-Tyr-Gly-Arg- (Lys) 2_ (Arg) 2 -Gln-(Arg) 3-NH2 ; (SEQ ID NO : 136)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Tyr-Gly-Arg-(Lys) 2-Arg-G In- (Arg) 4-NH2 ； (SEQ ID NO : 137)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-Arg-(Lys) 2_ (Arg) 2_G1 n-(Arg)3-NH2 ； (SEQ ID NO 136)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 138)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Gly- (Arg) 5_Gln_ (Arg) 3_N H2 ； (SEQ ID NO 138)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Tyr-Gly- (Arg) 5-Gln- (Arg) 3 -NH2 ;_(SEQ ID NO 139)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Gly- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 140)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) _ β -Ala-Tyr-Gly- (Arg) 2-Lys- (Arg) 2 -Gln-(Arg) 3-NH2 ； (SEQ ID NO 141)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Tyr-Gly-Arg-Lys- (Arg) 3_G In- (Arg) 3-ΝΗ2 ； (SEQ ID NO : 142)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Gly- (Arg) 2-Lys- (Arg) 2-Gln -(Arg)3-NH2 ； (SEQ ID NO 141)Ac-Nle-c(Cys-D-Ala-His-D-Ph e-Arg-Trp-Cys)- β -Ala-Gly-Arg-Lys-(Arg) 3-Gln-( Arg) 3-NH2 ； (SEQ ID NO 142)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala- (Arg) 2-Lys- (Arg) 2_Gln- (Ar g) 3-NH2 ； (SEQ ID NO 143)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Arg-Lys- (Arg) 3-Gln- (Arg) 3 -NH2 ； (SEQ ID NO 144)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 148)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - ( β -Ala) 2- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 148)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - ( β -Ala) 2-Gly- (Arg) 5_Gln_ (Arg) 3-NH2 ；(SEQ ID NO 149)；Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - ( β -Ala) 2-Tyr-Gly- (Arg) 5_Gln_ (Ar g) 3-NH2 ;_(SEQ ID NO 149)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) -Doc- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 151)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) -Doc-Gly- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 150)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg) 5_Gln_ (Arg) 3_N H2 ； (SEQ ID NO 150)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - (Doc) 2- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 151)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - (Doc) 2-Gly- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 152)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - (Doc) 2-Tyr-Gly- (Arg) 5-Gln- (Arg) 3 -NH2 ；(SEQ ID NO 152)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 154)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - β -Ala-Tyr-Gly- (Arg) 5-Gln- (Arg) 4 -NH2 ;_(SEQ ID NO 153)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - ( β -Ala) 2- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 154)11Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - ( β -Ala) 2-Gly- (Arg) 5_Gln_ (Arg) 4-NH2 ；(SEQ ID NO 155)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - ( β -Ala) 2-Tyr-Gly- (Arg) 5_Gln_ (Ar g) 4-NH2 ； (SEQ ID NO 155)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) -Doc- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 157)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) -Doc-Gly- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 156)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg) 5_Gln_ (Arg) 4_N H2 ； (SEQ ID NO 156)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - (Doc) 2- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 157)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - (Doc) 2-Gly- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 158)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) - (Doc) 2-Tyr-Gly- (Arg) 5-Gln- (Arg) 4 -NH2 ；(SEQ ID NO 158)Ac-Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - β -Ala-Tyr-Gly- (Arg) 5-Gln- (Arg) 3-NH2 ；(SEQ ID NO 159)Ac-Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 160)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Ala-Lys) - β -Ala-Tyr-Gly- (Arg)「Gin- (Arg)「N H2 ； (SEQ ID NO 161)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Ala-Lys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 162)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - β -Ala-Tyr-Gly- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 164)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - β -Ala-Gly- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 163)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 163)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - ( β -Ala) 2-Tyr-Gly- (Arg) 5_Gln_ (Arg) 3_N H2 ； (SEQ ID NO 164)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - ( β -Ala) 2-Gly- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 165)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - ( β -Ala) 2- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 165)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) -Doc-Tyr-Gly- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 166)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) -Doc-Gly- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ IDNO 166)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) -Doc- (Arg) 5-Gln- (Arg) 3"NH2 ； (SEQID NO 168)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - (Doc) 2-Tyr-Gly- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 167)Ac-Nle-c (Asp-His-D-Ph e-Arg-Trp-Lys) - (Doc) 2-Gly- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 167)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - (Doc) 2- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 168)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - β -Ala-Tyr-Gly- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 170)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - β -Ala-Gly- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 169)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - β -Ala- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 169)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - ( β -Ala) 2-Tyr-Gly- (Arg) 5_Gln_ (Arg) 4_N H2 ； (SEQ ID NO 170)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - ( β -Ala) 2-Gly- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 171)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - ( β -Ala) 2- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 171)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) -Doc-Tyr-Gly- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 173)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) -Doc-Gly- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 172)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) -Doc- (Arg) 5-Gln- (Arg) 4-NH2 ； (SEQID NO 172)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - (Doc) 2-Tyr-Gly- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 173)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - (Doc) 2-Gly- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 174)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Lys) - (Doc) 2- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 174)Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β -Ala-Lys)- β -Ala-Tyr-Gly-(Arg) 5-Gln- (Arg )3-NH2 ； (SEQ ID NO 175)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp- β -Ala-Lys) - β -Ala- (Arg) 5_Gln- (Arg) 3_NH2 ； (SEQ ID NO 176)Ac-Nle-c (Cys-His-D-Phe-Arg-Trp-Ahx-Cys) - β -Ala-Tyr-Gly- (Arg) 5-Gln- (Arg) 3_N H2 ； (SEQ ID NO 177)Ac-Nle-c (Cys-His-D-Phe-Arg-Trp-Ahx-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 178)D-Phe-c(Cys-His-D-Phe-Arg-Trp-β -Ala-D-Cys)-Thr- β -Ala-Tyr-Gly- (Arg) 5-Gln -(Arg)3-NH2 ； (SEQ ID NO 179)D-Phe-c (Cys-His-D-Phe-Arg-Trp- β -Ala-D-Cys) -Thr- β -Ala- (Arg) 5_Gln_ (Arg)「N H2 ；(SEQ ID NO 180)Ac-Nle-c (Cys-His-D-Ph e-Arg-Trp-Apn-Cys) - β -Ala-Tyr-Gly- (Arg) 5-Gln- (Arg) 3-NH2 ；(SEQ ID NO 181)Ac-Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 182)Ac-Cha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala-Tyr-Gly- (Arg) 5-Gln- (Arg) 3-NH2 ；(SEQ ID NO 183)Ac-Cha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 184)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala-Tyr-Gly- (Arg) 5-Gln- (Arg) 3-NH2 ；(SEQ ID NO 183)Ac-Nle-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 185)Ac-Chg-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala-Tyr-Gly- (Arg) 5-Gln- (Arg) 3-NH2 ；(SEQ ID NO 186)Ac-Chg-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 185)Ac-hCha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala-Tyr-Gly- (Arg) 5-Gln- (Arg) 3 -NH2 ； (SEQ ID NO 186)Ac-hCha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala- (Arg) 5_Gln- (Arg) 3_NH2 ； (SEQ ID NO 188)Ac-hCha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - ( β -Ala) 2-Tyr-Gly- (Arg) 5-Gln- (Ar g) 3-NH2 ； (SEQ ID NO 187)Ac-hCha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - ( β -Ala) 2- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 188)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg) 5_Gln_ (Arg) 3_N H2 ；(SEQ ID NO 189)Ac-hCha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) -Doc- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 190)Ac-hCha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - (Doc) 2-Tyr-Gly- (Arg) 5-Gln- (Arg) 3 -NH2 ； (SEQ ID NO 189)Ac-hCha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - (Doc) 2_ (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 190)Ac-hCha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - β -Ala-Tyr-Gly- (Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO 191)Ac-hCha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - & -Ala- (Arg) 5_Gln- (Arg) 4_NH2 ； (SEQ ID NO 192)Ac-hCha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - ( 3 -Ala) 2-Tyr-Gly- (Arg) 5-Gln- (Ar g) 4-NH2 ； (SEQ ID NO 191)Ac-hCha-c (Asp-Hi s-D-Phe-Arg-Trp-Gaba-Lys) - ( 3 -Ala) 2- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 192)Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg) 5_Gln_ (Arg) 4_N H2 ;_(SEQ ID NO 193)Ac-hCha-c (Asp-Hi s-D-Phe-Arg-Trp-Gaba-Lys) -Doc- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 194)Ac-hCha-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - (Doc) 2-Tyr-Gly- (Arg) 5_Gln_ (Arg) 4 -NH2 ；(SEQ ID NO 193)Ac-hCha-c (Asp-Hi s-D-Phe-Arg-Trp-Gaba-Lys) - (Doc) 2- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 194)Ac-D-Chg-c (Asp-His-D-Ph e-Arg-Trp-Gaba-Lys)- 3 -Ala-Tyr-Gly-(Arg)「Gin- (Arg )3-NH2 ； (SEQ ID NO 195)Ac-D-Chg-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - & -Ala- (Arg) 5_Gln- (Arg) 3_NH2 ； (SEQ ID NO 196)Ac-hPhe-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - 3 -Ala-Tyr-Gly- (Arg)「Gin- (Arg) 3 -NH2 ；(SEQ ID NO 197)Ac-hPhe-c (Asp-His-D-Phe-Arg-Trp-Gaba-Lys) - 3 -Ala- (Arg) 5_Gln- (Arg) 3_NH2 ； (SEQ ID NO 198)Ac-Nle-c (Cys-His-D-Phe-Arg-D-Trp-Apn-Cys) - 3 -Ala-Tyr-Gly- (Arg)「Gin- (Arg) 3 -NH2 ;_(SEQ ID NO 199)Ac-Nle-c (Cys-His-D-Phe-Arg-D-Trp-Apn-Cys) - 3 -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 200)Ac-Nle-c (Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys) - 3 -Ala-Tyr-Gly- (Arg)「Gin- (Arg) 3 -NH2 ;_(SEQ ID NO 199)Ac-Nle-c (Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys) - 3 -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 200)Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-3 -Ala-Cys)-3 -Ala-Tyr-Gly- (Arg) 5_Gln_ (A rg) 3-NH2 ； (SEQ ID NO 201)Ac-Nle-c (Cys-His-D-Ph e-Arg-D-Trp-3 -Ala-Cys) - 3 -Ala-(Arg) 5_Gln_ (Arg) 3_N H2 ； (SEQ ID NO 202)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) - 3 -la-Tyr-Gly- (Arg)「Gin- (Arg) 3-NH2 ;_(SEQ ID NO 203)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) - 3 -Ala-Gly- (Arg) 5_Gln_ (Arg) 3_N H2 ； (SEQ ID NO 203)15Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) - & -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 205)Ac-Nle-c (Cys-D-Ala-His-D-Ph e-Arg-Trp-Pen) - ( 3 -Ala) 2-Tyr-Gly- (Arg) 5_Gln_ (A rg) 3-NH2 ； (SEQ ID NO 204)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) - ( 3 -Ala) 2-Gly- (Arg) 5_Gln_ (Arg) 3-NH2 ； (SEQ ID NO 204)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) - ( 3 -Ala) 2- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 205)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Tyr-Gly-(Arg) 5_Gln_ (Arg) 3_N H2 ;_(SEQ ID NO 207)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) -Doc-Gly- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 206)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) -Doc- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 206)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) - (Doc) 2-Tyr-Gly- (Arg) 5_Gln_ (Arg) 3 -NH2 ；(SEQ ID NO 207)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) - (Doc) 2-Gly- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 208)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen) - (Doc) 2- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 208)D-Phe-c(Cys-His-D- (Et)Tyr-Arg-Trp-3 -Ala-D-Cys)-3 -Ala-Tyr-Gly-(Arg)「Gin -(Arg) 3-NH2 ； (SEQ ID NO 209)D-Phe-c (Cys-His-D- (Et) Tyr-Arg-Trp- 3 -Ala-D-Cys) - 3 -Ala- (Arg) 5_Gln_ (Arg)「N H2 ；(SEQ ID NO 210)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-3 -Ala-D-Cys)-3 -Ala-Gly- (Arg) 5_Gln_ (Ar g) 3-NH2 ； (SEQ ID NO 209)D-Phe-c (Cys-His-D- (Et) Tyr-Arg-Trp- 3 -Ala-D-Cys) - 3 -Ala- (Arg) 5_Gln_ (Arg) 4_N H2 ；(SEQ ID NO 211)D-Ph e-c (Cys-His-D- (Et) Tyr-Arg-Trp- 3 -Ala-D-Cys) - ( 3 -Ala) 2-Tyr-Gly- (Arg) 5-Gln-(Arg) 3-NH2 ; (SEQ ID NO 212)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-3 -Ala-D-Cys)-(3 -Ala) 2- (Arg) 5_Gln_ (Arg)3-NH2； (SEQ ID NO 213)D-Phe-c (Cys-His-D- (Et) Tyr-Arg-Trp- 3 -Ala-D-Cys) - ( 3 -Ala) 2-Gly- (Arg) 5_Gln_ ( Arg) 3-NH2 ； (SEQ ID NO : 213)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-3 -Ala-D-Cys)-(3 -Ala) 2- (Arg) 5_Gln_ (Arg)4-NH2； (SEQ ID NO 267)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-3 -Ala-D-Cys)-Doc-Tyr-Gly-(Arg) 5_Gln_ (A rg) 3-NH2 ； (SEQ ID NO 214)D-Phe-c (Cys-His-D- (Et) Tyr-Arg-Trp- 3 -Ala-D-Cys) -Doc- (Arg) 5_Gln_ (Arg) 3_NH2 ；(SEQ ID NO 216)D-Phe-c (Cys-His-D- (Et) Tyr-Arg-Trp- 3 -Ala-D-Cys) -Doc-Gly- (Arg)「Gin- (Arg) 3-NH2 ;_(SEQ ID NO 214)D-Phe-c (Cys-His-D- (Et) Tyr-Arg-Trp- 3 -Ala-D-Cys) -Doc- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 217)D-Phe-c (Cys-His-D- (Et) Tyr-Arg-Trp- 3 -Ala-D-Cys) - (Doc) 2-Tyr-Gly- (Arg) 5-Gln-(Arg) 3-NH2 ； (SEQ ID NO : 215)D-Phe-c (Cys-Hi s_D_ (Et) Tyr-Arg-Trp- 3 -Ala-D-Cys) - (Doc) 2- (Arg) 5_Gln_ (Arg) 3_N H2 ；(SEQ ID NO 216)D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-3 -Ala-D-Cys)-(Doc)2-Gly-(Arg) 5_Gln_(Arg )3-NH2 ； (SEQ ID NO : 215)D-Phe-c (Cys-Hi s_D_ (Et) Tyr-Arg-Trp- 3 -Ala-D-Cys) - (Doc) 2- (Arg) 5_Gln_ (Arg) 4_N H2 ； (SEQ ID NO 217)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-3 -Ala-D-Cys)_Thr_ 3 -Ala-Tyr-Gly- (Arg) 5-Gln-(Arg) 3-NH2 ； (SEQ ID NO 218)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-3 -Ala-D-Cys)_Thr_ 3 -Ala- (Arg) 5_Gln_ (A rg) 3-NH2 ； (SEQ ID NO 219)D-Phe-c (Cys-His_D_ (Et) Tyr-hArg-Trp- 3 -Ala-D-Cys) _Thr_ ( 3 -Ala) 2-Tyr-Gly- (A rg) 5-Gln-(Arg) 3-NH2 ； (SEQ ID NO 218)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-3 -Ala-D-Cys)_Thr_(3 -Ala) 2- (Arg) 5_Gln_ (Arg) 3-NH2 ； (SEQ ID NO 219)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-3 -Ala-D-Cys)-Thr-Doc-Tyr-Gly- (Arg) 5_G In-(Arg) 3-NH2 ； (SEQ ID NO 221)D-Phe-c (Cys-His-D- (Et) Tyr-hArg-Trp- 3 -Ala-D-Cys) -Thr-Doc- (Arg)「Gin- (Arg) 3 -NH2 ； (SEQ ID NO 220)D-Phe-c (Cys-His-D- (Et) Tyr-hArg-Trp- 3 -Ala-D-Cys) _Thr_ (Doc) 2-Tyr-Gly- (Arg) 5 -Gin-(Arg) 3-NH2 ; (SEQ ID NO 221)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-3 -Ala-D-Cys)_Thr_ 3 -Ala-Tyr-Gly- (Arg) 5-Gln-(Arg)4-NH2 ； (SEQ ID NO 222)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-3 -Ala-D-Cys)_Thr_ 3 -Ala- (Arg) 5_Gln_ (A rg)4-NH2 ； (SEQ ID NO 223)D-Phe-c (Cys-His-D- (Et) Tyr-hArg-Trp- 3 -Ala-D-Cys) _Thr_ ( 3 -Ala) 2-Tyr-Gly- (A rg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO : 222)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-3 -Ala-D-Cys)_Thr_(3 -Ala) 2- (Arg) 5_Gln_ (Arg)4-NH2 ； (SEQ ID NO 223)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-3 -Ala-D-Cys)-Thr-Doc-Tyr-Gly- (Arg) 5_G In-(Arg)4-NH2 ； (SEQ ID NO 224)D-Phe-c (Cys-His-D- (Et) Tyr-hArg-Trp- 3 -Ala-D-Cys) -Thr-Doc- (Arg)「Gin- (Arg) 4 -NH2 ;_(SEQ ID NO 225)17D-Phe-c (Cys-His-D- (Et) Tyr-hArg-Trp- 3 -Ala-D-Cys) _Thr_ (Doc) 2-Tyr-Gly- (Arg) 5 -Gin-(Arg) 4-NH2 ; (SEQ ID NO : 224)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-3 -Ala-D-Cys)_Thr_(Doc) 2-(Arg) 5_Gln_(Ar g)4-NH2 ;_(SEQ ID NO 225)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-3 -Ala-D-Cys)_Thr_ 3 -Ala-Tyr-Gly- (Arg) 5-Gln-(Arg) 3-NH2 ； (SEQ ID NO 227)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-3 -Ala-D-Cys)_Thr_ 3 -Ala-Tyr-Gly- (Arg) 5-Gln-(Arg)4-NH2 ； (SEQ ID NO 226)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-3 -Ala-D-Cys)_Thr_ 3 -Ala- (Arg) 5_Gln_ (A rg) 3-NH2 ； (SEQ ID NO 228)D-Phe-c (Cys-His-D- (Et) Tyr-hArg-Bip- 3 -Ala-D-Cys) _Thr_ ( 3 -Ala) 2-Tyr-Gly- (A rg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO : 227)D-Ph e-c(Cys-His-D-(Et)Tyr-hArg-Bip-3 -Ala-D-Cys)_Thr_(3 -Ala)2-(Arg)「Gin -(Arg) 3-NH2 ； (SEQ ID NO 228)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-3 -Ala-D-Cys)-Thr-Doc-Tyr-Gly- (Arg) 5_G In-(Arg) 3-NH2 ； (SEQ ID NO 229)D-Ph e-c(Cys-His-D-(Et)Tyr-hArg-Bip-3 -Ala-D-Cys)-Thr-Doc-Tyr-Gly-(Arg) 5_G In-(Arg)4-NH2 ； (SEQ ID NO 230)D-Phe-c (Cys-His-D- (Et) Tyr-hArg-Bip- 3 -Ala-D-Cys) -Thr-Doc- (Arg) 5_Gln_ (Arg) 3 -NH2 ;_(SEQ ID NO 232)D-Phe-c (Cys-His-D- (Et) Tyr-hArg-Bip- 3 -Ala-D-Cys) _Thr_ (Doc) 2-Tyr-Gly- (Arg) 5 -Gin-(Arg) 3-NH2 ; (SEQ ID NO 231)D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-3 -Ala-D-Cys)_Thr_(Doc) 2-(Arg) 5_Gln_(Ar g) 3-NH2 ； (SEQ ID NO 232)Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)- 3 -Ala-Tyr-Gly- (Arg) 5_Gln_ ( Arg) 3-NH2 ； (SEQ ID NO 233)Ac-Nle-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys) - 3 -Ala- (Arg) 5_Gln_ (Arg) 3_N H2 ； (SEQ ID NO 234)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys) - 3 -Ala-Tyr-Gly- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 235)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys) - 3 -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 236)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys) - ( 3 -Ala) 2-Tyr-Gly- (Arg) 5_Gln_ (Arg) 3_N H2 ；(SEQ ID NO 235)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys) - ( ^ -Ala)2- (Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO 236)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys) - 3 -Ala-Tyr-Gly- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 237)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys) - 3 -Ala- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ IDNO 238)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys) - ( 3 -Ala) 2-Tyr-Gly- (Arg) 5_Gln_ (Arg) 4_N H2 ；(SEQ ID NO 237)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(3 -Ala)2-(Arg)5-Gln-(Arg)4-NH2 ； (SEQ ID NO 238)Nle-c (Cys-His-D-Ph e-Arg-Trp-Apn-Cys) -Doc-Tyr-Gly- (Arg) 5_Gln_ (Arg) 3-NH2 ； (SEQ ID NO 239)Nle-c (Cys-His-D-Ph e-Arg-Trp-Apn-Cys) -Doc- (Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO:240)Nle-c (Cys-His-D-Ph e_Arg_Trp-Apn_Cys) _ (Doc) 2_Tyr_Gly_ (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 239)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-(Arg) 5-Gln-(Arg)3-NH2 ； (SEQ ID NO 240)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys) -Doc-Tyr-Gly- (Arg) 5_Gln_ (Arg) 4-NH2 ； (SEQ ID NO 241)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg) 5-Gln-(Arg) 4-NH2 ； (SEQ ID NO 242)Nle-c (Cys-Hi s-D-Phe-Arg-Trp-Apn-Cys) - (Doc) 2-Tyr-Gly- (Arg) 5_Gln_ (Arg) 4-NH2 ； (SEQ ID NO 241)Nle-c (Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-(Arg) 5-Gln-(Arg)4-NH2 ； (SEQ ID NO 242)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - 3 -Ala-Tyr-Gly- (Arg)「Gin- (Arg) 3 -NH2 ； (SEQ ID NO 243)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - 3 -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 244)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - ( 3 -Ala) 2-Tyr-Gly- (Arg) 5-Gln- (Ar g) 3-NH2 ； (SEQ ID NO 243)Ac-Nle-c (Cys-D-Leu-His-D-Ph e-Arg-Trp-Cys) - ( 3 -Ala) 2- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 244)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg) 5_Gln_ (Arg) 3_N H2 ;_(SEQ ID NO 245)Ac-Nle-c (Cys-D-Leu-His-D-Ph e-Arg-Trp-Cys)-Doc-(Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 246)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - (Doc) 2-Tyr-Gly- (Arg) 5_Gln_ (Arg) 3 -NH2 ;_(SEQ ID NO 245)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - (Doc) 2- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 246)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - 3 -Ala-Tyr-Gly- (Arg)「Gin- (Arg) 4 -NH2 ； (SEQ ID NO 247)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - & -Ala- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 248)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - ( 3 -Ala) 2-Tyr-Gly- (Arg) 5-Gln- (Ar g)4-NH2 ； (SEQ ID NO 247)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - ( 3 -Ala) 2- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 248)Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg) 5_Gln_ (Arg) 4_N H2 ； (SEQ ID NO 249)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) -Doc- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 250)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - (Doc) 2-Tyr-Gly- (Arg) 5_Gln_ (Arg) 4 -NH2 ； (SEQ ID NO 249)Ac-Nle-c (Cys-D-Leu-His-D-Phe-Arg-Trp-Cys) - (Doc) 2- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 250)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - 3 -Ala-Tyr-Gly- (Arg)「Gin- (Arg) 3 -NH2 ； (SEQ ID NO 251)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - 3 -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 252)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - ( 3 -Ala) 2-Tyr-Gly- (Arg) 5_Gln_ (Ar g) 3-NH2 ； (SEQ ID NO 251)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - ( 3 -Ala) 2- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 252)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg) 5_Gln_ (Arg) 3_N H2 ;_(SEQ ID NO 253)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) -Doc- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 254)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - (Doc) 2-Tyr-Gly- (Arg) 5_Gln_ (Arg) 3 -NH2 ； (SEQ ID NO 253)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - (Doc) 2- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 254)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - 3 -Ala-Tyr-Gly- (Arg)「Gin- (Arg) 4 -NH2 ； (SEQ ID NO 255)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - 3 -Ala- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 256)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - ( 3 -Ala) 2-Tyr-Gly- (Arg) 5_Gln_ (Ar g)4-NH2 ； (SEQ ID NO 255)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - ( 3 -Ala) 2- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 256)Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg) 5_Gln_ (Arg) 4_NH2 ;_(SEQ ID NO 257)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) -Doc- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 258)Ac-Nle-c (Cys_D_Cha_His_D_Phe_Arg_Trp_Cys) _ (Doc) 2_Tyr_Gly_ (Arg) 5_Gln_ (Arg) 4 -NH2 ； (SEQ ID NO 257)Ac-Nle-c (Cys-D-Cha-His-D-Phe-Arg-Trp-Cys) - (Doc) 2- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 258)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - 3 -Ala-Tyr-Gly- (Arg) 5_Gln_ (Arg) 3_N H2 ；(SEQ ID NO 259)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) _ 3 -Ala- (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 260)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - ( 3 -Ala) 2-Tyr-Gly- (Arg) 5_Gln_ (Arg) 3-NH2 ；(SEQ ID NO 259)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) _ ( 3 -Ala) 2_ (Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 260)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - 3 -Ala-Tyr-Gly- (Arg) 5_Gln_ (Arg) 4_N H2 ； (SEQ ID NO 261)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) _ 3 -Ala- (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 262)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - ( 3 -Ala) 2-Tyr-Gly- (Arg) 5_Gln_ (Arg) 4-NH2 ；(SEQ ID NO 261)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) _ ( 3 -Ala) 2_ (Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 262)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) -Doc-Tyr-Gly- (Arg) 5_Gln_ (Arg) 3-NH2 ； (SEQ ID NO 263)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) -Doc-(Arg) 5_Gln_ (Arg) 3_NH2 ； (SEQ ID NO 264)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - (Doc) 2-Tyr-Gly- (Arg) 5-Gln- (Arg) 3-NH2 ； (SEQ ID NO 263)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2 ； (SEQ ID NO 264)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) -Doc-Tyr-Gly- (Arg) 5_Gln_ (Arg) 4-NH2 ； (SEQ ID NO 265)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) -Doc-(Arg) 5_Gln_ (Arg) 4_NH2 ； (SEQ ID NO 266)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys) - (Doc)2-Tyr-Gly- (Arg) 5-Gln- (Arg) 4-NH2 ； (SEQ ID NO 265)Nle-c (Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2 ； (SEQ ID NO 266)Ac-c (Cys-Glu-His-D-4-Br-Phe-Arg-Trp-Gly-Cys)-(Pro)2-Lys-Asp-NH2 ； (SEQ ID NO 268)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro) 2-Lys-Asp-NH2 ； (SEQID NO 269)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys) - (Pro) 2-Lys-Asp-NH2 ； (SEQID NO 269)Ac-c (Cys-Glu-His-D-2-Nal-Arg-l-Nal-Ala-Cys) - (Pro) 2-Lys-Asp-NH2 ； (SEQID NO 269)Ac-c (Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys) - (Pro) 2-Lys-Asp-NH2 ； (SEQID NO 210)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-3 -Ala-Cys) - (Pro) 2-Lys-Asp-NH2 ； (SEQ ID NO 270)Ac-c (Cys-Glu-His-D-2-Nal-Arg-2-Nal-Aib-Cys) - (Pro) 2-Lys-Asp-NH2 ； (SEQID NO 270)c[乙内酰脲(C(0)-(Cys-D-Ala))-His-D-Phe_Arg-Trp-Cys]-NH2 ； (SEQ IDNO 271) c[乙内酰脲(C(0)-(hCys-D-Ala))-His-D-Phe_Arg-Trp-Cys]-NH2 ； (SEQ IDNO 271) c[乙内酰脲(C(0)-(Cys-D-Ala))-His-D-2-Nal-Arg-Trp-Cys]-NH2 ； (SEQ IDNO 272) c [乙内酰脲(C (0) - (hCys-D-Ala)) -His-D-2-Nal-Arg-Trp-Cys] _NH2 ； (SEQ IDNO 272) c [乙内酰脲(C(0)-(Asp-D-Ala))-His-D-Phe_Arg-Trp-Lys]-NH2 ； (SEQ IDNO 273) c[乙内酰脲(C(0)-(Asp-D-Ala))-His-D-Phe_Arg-Trp-0rn]-NH2 ； (SEQ IDNO 273) c[乙内酰脲(C(0)-(Asp-D-Ala))-His-D-Phe_Arg-Trp-Dab]-NH2 ； (SEQ IDNO 273) c[乙内酰脲(C(0)-(Asp-D-Ala))-His-D-Phe_Arg-Trp-Dap]-NH2 ； (SEQ IDNO 273) c[乙内酰脲(C(0)-(Asp-His))-D-2-Nal-Arg-Trp-Lys]-NH2 ； (SEQ IDNO 275) c[乙内酰脲(C(0)_(Asp-His))-D-Phe-Arg-Trp-Lys]-NH2 ； (SEQ ID NO 274) c[乙内酰脲(C(0)-(Asp-A3c))-D-Phe-Arg-Trp-Lys]-NH2 ； (SEQ ID NO 274) c[乙内酰脲(C(0)-(Asp-A5c))-D-Phe-Arg-Trp-Lys]-NH2 ； (SEQ ID NO 274) c[乙内酰脲(C(0)-(Asp-A6c))-D-Phe-Arg-Trp-Lys]-NH2 ； (SEQ ID NO 274) c[乙内酰脲(C(0)-(Asp-A3c))-D-2-Nal-Arg-Trp-Lys]-NH2 ； (SEQ IDNO 275) c[乙内酰脲(C(0)-(Asp-A5c))-D-2-Nal-Arg-Trp-Lys]-NH2 ； (SEQ IDNO 275) c[乙内酰脲(C(0)-(Asp-A6c))-D-2-Nal-Arg-Trp-Lys]-NH2 ； (SEQ IDNO 275) c[乙内酰脲(C(0)-(Asp-A5c))-D-2-Nal-Arg-Trp-Lys]-NH2 ； (SEQ IDNO 275) c[乙内酰脲(C(O)-(Asp-Aic))-D-Phe-Arg-Trp-Lys]-NH2 ； (SEQ ID NO 274) c[乙内酰脲(C(0)-(Asp-Ape))-D-Phe-Arg-Trp-Lys]-NH2 ； (SEQ ID NO 274) c[乙内酰脲(C(0)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NH2 ； (SEQ IDNO 275) c[乙内酰脲(C(0)_(Asp-Ape))-D-2-Nal-Arg-Trp-Lys]-NH2 ； (SEQ IDNO 275) c [乙内酰脲-(C (0) - (Asp-Aic)) -D-2-Nal-Arg-Trp-Lys] _NH2 ； (SEQ IDNO 275) c [乙内酰脲-(C (0) - (Asp-Ape)) -D-2-Nal-Arg-Trp-Lys] _NH2 ； (SEQ IDNO 275) c[乙内酰脲(C(0)-(Glu-D-Ala))-His-D-Phe_Arg-Trp-0rn]-NH2 ； (SEQ IDNO 276) c[乙内酰脲(C(0)-(Glu-D-Ala))-His-D-Phe_Arg-Trp-Dab]-NH2 ； (SEQ IDNO 276)c[乙内酰脲(C(0)-(Glu-D-Ala))-His-D-Phe_Arg-Trp-Dap]-NH2 ； (SEQ IDN0 276) c[乙内酰脲(C(0)-(Glu-His))-D-Phe_Arg-Trp-Dap]-NH2 ； (SEQ IDN0 277) 乙内酰脲(C(0)-(Arg-Gly))-c(Cys-Glu-His-D_Phe-Arg-Trp-Cys)-NH2 ； (SEQ ID NO:278)乙内酰脲(C (0) - (Nle-Gly)) _c (Cys-Glu-His-D-Phe-Arg-Trp-Cys) _NH2 ； (SEQID NO 278)乙内酰脲(C(0)_(Gly-Gly))-c(Cys-Glu-His-D-Phe_Arg-Trp-Cys)-NH2 ； (SEQID NO 278)乙内酰脲(C (0)-(Nle-Gly))-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ; (SEQ ID NO 279)乙内酰脲(C(0)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe_Arg-Trp-Cys)-NH2 ; (SEQ ID NO 279)乙内酰脲(C (0)-(Nle-Gly))-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2 ; (SEQ ID NO 280)乙内酰脲(C(0)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe_Arg-Trp-Pen)-NH2 ; (SEQ ID NO 280)乙内酰脲(C(0)-(Ala-Gly))-c(Cys-D-Ala-His-D-Phe_Arg-Trp-Cys)-NH2 ; (SEQ ID NO 279)乙内酰脲(C (0) - (D-Ala-Gly)) _c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) _NH2 ； (SEQ ID NO 279)乙内酰脲(C(0)-(Aib-Gly))-c(Cys-D-Ala-His-D-Phe_Arg-Trp-Cys)-NH2 ; (SEQ ID NO 279)乙内酰脲(C(0)-(Val-Gly))-c(Cys-D-Ala-His-D-Phe_Arg-Trp-Cys)-NH2 ; (SEQ ID NO 279)乙内酰脲(C(0)-(Ile-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ； (SEQ ID NO 279)乙内酰脲(C(0)-(Leu-Gly))-c(Cys-D-Ala-His-D-Phe_Arg-Trp-Cys)-NH2 ; (SEQ ID NO 279)乙内酰脲(C(0)-(Gly-Gly))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2 ; (SEQ ID NO 281)乙内酰脲(C (0)-(Nle-Gly))-c (Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2 ; (SEQ ID NO 281)乙内酰脲(C(0)-(D-Arg-Gly))-c(Cys-Glu-His-D_Phe-Arg-Trp-Cys)-NH2 ； (SEQ ID NO 278)乙内酰脲(C (0) - (D-Arg-Gly)) _c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) _NH2 ； (SEQ ID NO 279)乙内酰脲(C(0)-(Arg-Gly))-c(Cys-D-Ala-His-D_Phe-Arg-Trp-Cys)-NH2 ； (SEQ ID NO 279)乙内酰脲(C (0) - (D-Arg-Gly)) _c (Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys) -NH2 ； (SEQID NO 282)乙内酰脲(C (0) - (Arg-Gly)) _c (Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys) -NH2 ； (SEQ ID NO 282)乙内酰脲(C (0) - (Ala-Nle)) _c (Cys-Glu-His-D-Phe-Arg-Trp-Cys) _NH2 ； (SEQID NO 283)乙内酰脲(C(0)_(Val-Nle))-c(Cys-Glu-His-D-Phe_Arg-Trp-Cys)-NH2 ； (SEQID NO 283)乙内酰脲(C(0)_(Gly-Nle))-c(Cys-Glu-His-D-Phe_Arg-Trp-Cys)-NH2 ； (SEQID NO 283)乙内酰脲(C(0)-(A6c-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ; (SEQ ID NO 284)乙内酰脲(C(0)-(Gly-Nle))-c(Cys-D-Ala-His-D-Phe_Arg-Trp-Cys)-NH2 ; (SEQ ID NO 284)乙内酰脲(C (0)-(Ala-Nle))-c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ; (SEQ ID NO 284)乙内酰脲(C (0) - (D-Ala-Nle)) _c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) _NH2 ； (SEQ ID NO 284)乙内酰脲(C(0)-(Val-Nle))-c(Cys-D-Ala-His-D-Phe_Arg-Trp-Cys)-NH2 ; (SEQ ID NO 284)乙内酰脲(C(0)-(Leu-Nle))-c(Cys-D-Ala-His-D-Phe_Arg-Trp-Cys)-NH2 ; (SEQ ID NO 284)乙内酰脲(C(0)-(Cha-Nle))-c(Cys-D-Ala-His-D_Phe-Arg-Trp-Cys)-NH2 ； (SEQ ID NO 284)乙内酰脲(C(0)-(Aib-Nle))-c(Cys-D-Ala-His-D-Phe_Arg-Trp-Cys)-NH2 ; (SEQ ID NO 284)乙内酰脲(C(0)-(Gly-Arg))-c(Cys-Glu-His-D_Phe-Arg-Trp-Cys)-NH2 ; (SEQ ID NO:285)乙内酰脲(C(0)-(Gly-Arg))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2 ; (SEQ ID NO 285)乙内酰脲(C(0)-(Gly-Arg))-c(Cys-D-Ala-His-D_Phe-Arg-Trp-Cys)-NH2 ； (SEQ ID NO 286)乙内酰脲(C (0) - (Gly-Arg)) _c (Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys) -NH2 ； (SEQ ID NO 286)乙内酰脲(C(0)-(Gly-D-Arg))-c(Cys-Glu-His-D_Phe-Arg-Trp-Cys)-NH2 ； (SEQ ID NO 287)乙内酰脲(C (0) - (Gly-D-Arg)) _c (Cys-D-Ala-His-D-Phe-Arg-Trp-Cys) _NH2 ； (SEQ ID NO 288)乙内酰脲(C (0) - (Gly-D-Arg)) _c (Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys) -NH2 ； (SEQ ID NO 288)乙内酰脲(C(0)_(Nle-Ala))-c(Cys-Glu-His-D-Phe_Arg-Trp-Cys)-NH2 ； (SEQID NO 289)c[乙内酰脲(C(0)-(Ala-Cys))-D-Ala-His-D-Phe_Arg-Trp-Cys]-NH2，(SEQID NO:290)c[乙内酰脲(C(0)-(Nle-Cys))-D-Ala-His-D-Phe_Arg-Trp-Cys]-NH2 ； (SEQID NO:290)c [乙内酰脲(C(0)-(D-Ala-Cys))-D-Ala-His-D-Phe_Arg-Trp-Cys]-NH2 ； (SEQ ID NO 290)c[乙内酰脲290)c[乙内酰脲290)c[乙内酰脲290)c[乙内酰脲290)c [乙内酰脲290)c[乙内酰脲290)c[乙内酰脲290)c[乙内酰脲290)c[乙内酰脲290)c[乙内酰脲(C(0)-(Gly-Cys))-Glu-His-D-Phe_Arg-Trp-Cys]-NH2 ； (SEQ IDN0 291) Ac-Tyr-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ；(SEQ IDN0 292) Ac-2-Nal-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ；(SEQ IDN0 292) Ac-l-Nal-Arg-c(Cys-D-Ala-His-DPhe-Arg-Trp-Cys)-NH2 ；(SEQ IDN0 292) Ac-Phe-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ；(SEQ IDN0 292) Ac-Trp-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ；(SEQ IDN0 292) Ac-Pff-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ；(SEQ ID NO 292) H-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ；(SEQ ID NO :293) Ac-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2 ；(SEQ ID NO :292) 或其可药用盐。
3.根据权利要求2的方法，其中所述化合物是Ac-Arg-c(Cys-D-Ala-His-D-Ph e-Arg-Trp-Cys)-NH2 (SEQ ID NO 50)或其可药用盐。
4.根据权利要求2的方法，其中所述化合物是乙内酰脲(C(0)-(Arg-Gly))-C(CyS-Glu(C (O)-(Aib-Cys)(C (O)-(Val-Cys)(C(0)-(Abu-Cys)(C(0)-(Leu-Cys)(C(O)-(Ile-Cys)(C(0)-(Cha-Cys)(C(0)-(A6c-Cys)(C(0)-(Phe-Cys)(C(O)-(Gly-Cys)-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 ；(SEQID NO-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 ；(SEQID NO-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 ；(SEQID NO-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 ；(SEQID NO-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 ；(SEQ IDNO-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 ；(SEQID NO-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 ；(SEQID NO-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 ；(SEQID NO-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2 ；(SEQID NO-His-D-Phe-Arg-Trp-Cys) -NH2 (SEQ IDNO 278)或其可药用盐。
5.根据权利要求1-4任一项的方法，其中所述受试者是肥胖的。
6.根据权利要求1-4任一项的方法，其中所述受试者是超重的。
7.根据权利要求1-4任一项的方法，其中所述受试者是正常体重的。
8.根据权利要求1-4任一项的方法，其中所述的受试者是偏瘦的。
9.根据权利要求5的方法，其中所述肥胖的受试者罹患II型糖尿病。
10.根据权利要求6的方法，其中所述超重的受试者罹患II型糖尿病。
11.根据权利要求7的方法，其中所述正常体重的受试者罹患II型糖尿病。
12.根据权利要求8的方法，其中所述偏瘦的受试者罹患II型糖尿病。
13.根据权利要求1的方法，其中所述外周施用是经口、皮下、腹膜内、肌内、静脉内、直 肠、经皮或鼻内。
14.根据权利要求13的方法，其中所述施用是连续的、每小时的、每天四次、每天三次、每天两次、每天一次、每隔一天一次、每周两次、每周一次、每两周一次、每月一次，或每两月 一次。
15.根据权利要求14的方法，其中所述施用是连续的。
16.根据权利要求14的方法，其中所述施用是每天一次。
17.根据权利要求14的方法，其中所述施用是每周一次。
18.根据权利要求14的方法，其中所述施用是每两周一次。
19.根据权利要求14的方法，其中所述施用是每月一次。
20.根据权利要求14的方法，其中所述施用是每两月一次。
21.根据权利要求1-4任一项的方法，其中所述外周施用有效量的黑皮质素受体4激动 剂以治疗有其需要的受试者之所述胰岛素抵抗也降低所述有其需要的受试者之体重。
22.根据权利要求21的方法，其中所述化合物是Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg -Trp-Cys)-NH2 (SEQ ID NO 50)或其可药用盐。
23.根据权利要求21的方法，其中所述化合物是乙内酰脲(C(0)-(Arg-Gly))-c(CyS-G lu-His-D-Phe-Arg-Trp-Cys) -NH2 (SEQ IDNO 278)或其可药用盐。
24.根据权利要求21-23任一项的方法，其中所述受试者是肥胖的。
25.根据权利要求21-23任一项的方法，其中所述受试者是超重的。
26.根据权利要求24的方法，其中所述肥胖的受试者罹患II型糖尿病。
27.根据权利要求25的方法，其中所述超重的受试者罹患II型糖尿病。
28.根据权利要求21的方法，其中所述外周施用是经口、皮下、腹膜内、肌内、静脉内、 直肠、经皮或鼻内。
29.根据权利要求28的方法，其中所述的施用是连续的、每小时的、每天四次、每天三次、每天两次、每天一次、每隔一天一次、每周两次、每周一次、每两周一次、每月一次，或每 两月一次。
30.根据权利要求29的方法，其中所述施用是连续的。
31.根据权利要求29的方法，其中所述施用是每天一次。
32.根据权利要求29的方法，其中所述施用是每周一次。
33.根据权利要求29的方法，其中所述施用是每两周一次。
34.根据权利要求29的方法，其中所述施用是每月一次。
35.根据权利要求29的方法，其中所述施用是每两月一次。
全文摘要
本发明涉及黑皮质素受体(特别是黑皮质素4受体)的肽配体，其可用于治疗应答该受体的激活的病症，如胰岛素抵抗。
文档编号A61K38/00GK101980717SQ200880123893
公开日2011年2月23日 申请日期2008年11月5日 优先权日2007年11月5日
发明者A·A·巴特勒, H·A·哈勒姆, M·D·库勒 申请人:益普生制药股份有限公司;路易斯安那州州立大学及农业机械学院管理委员会