CN103316345B - 黑皮质素治疗胰岛素敏感的应用 - Google Patents
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- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- TWRXJAOTZQYOKJ-UHFFFAOYSA-L magnesium chloride Substances [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 1
- 229910001629 magnesium chloride Inorganic materials 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 239000001630 malic acid Substances 0.000 description 1
- 235000011090 malic acid Nutrition 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 210000002752 melanocyte Anatomy 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 239000004006 olive oil Substances 0.000 description 1
- 235000008390 olive oil Nutrition 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 230000008520 organization Effects 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 239000000813 peptide hormone Substances 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 1
- 239000010452 phosphate Substances 0.000 description 1
- 210000002826 placenta Anatomy 0.000 description 1
- 210000002381 plasma Anatomy 0.000 description 1
- 229920000747 poly(lactic acid) Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 239000004626 polylactic acid Substances 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920001155 polypropylene Polymers 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- ULWHHBHJGPPBCO-UHFFFAOYSA-N propane-1,1-diol Chemical group CCC(O)O ULWHHBHJGPPBCO-UHFFFAOYSA-N 0.000 description 1
- 238000011321 prophylaxis Methods 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 1
- 238000012797 qualification Methods 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000008261 resistance mechanism Effects 0.000 description 1
- 230000000630 rising effect Effects 0.000 description 1
- 229910052707 ruthenium Inorganic materials 0.000 description 1
- 238000009938 salting Methods 0.000 description 1
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical compound O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000007909 solid dosage form Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- KDYFGRWQOYBRFD-UHFFFAOYSA-L succinate(2-) Chemical compound [O-]C(=O)CCC([O-])=O KDYFGRWQOYBRFD-UHFFFAOYSA-L 0.000 description 1
- 229960005137 succinic acid Drugs 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
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- LRBQNJMCXXYXIU-NRMVVENXSA-N tannic acid Chemical compound OC1=C(O)C(O)=CC(C(=O)OC=2C(=C(O)C=C(C=2)C(=O)OC[C@@H]2[C@H]([C@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)[C@@H](OC(=O)C=3C=C(OC(=O)C=4C=C(O)C(O)=C(O)C=4)C(O)=C(O)C=3)O2)OC(=O)C=2C=C(OC(=O)C=3C=C(O)C(O)=C(O)C=3)C(O)=C(O)C=2)O)=C1 LRBQNJMCXXYXIU-NRMVVENXSA-N 0.000 description 1
- 229940033123 tannic acid Drugs 0.000 description 1
- 235000015523 tannic acid Nutrition 0.000 description 1
- 229920002258 tannic acid Polymers 0.000 description 1
- 229940095064 tartrate Drugs 0.000 description 1
- 125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 229950004288 tosilate Drugs 0.000 description 1
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 description 1
- 102000035160 transmembrane proteins Human genes 0.000 description 1
- 108091005703 transmembrane proteins Proteins 0.000 description 1
- ZGYICYBLPGRURT-UHFFFAOYSA-N tri(propan-2-yl)silicon Chemical compound CC(C)[Si](C(C)C)C(C)C ZGYICYBLPGRURT-UHFFFAOYSA-N 0.000 description 1
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 description 1
- UFTFJSFQGQCHQW-UHFFFAOYSA-N triformin Chemical compound O=COCC(OC=O)COC=O UFTFJSFQGQCHQW-UHFFFAOYSA-N 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
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- 238000005406 washing Methods 0.000 description 1
- 230000004580 weight loss Effects 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
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- A61K38/33—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans derived from pro-opiomelanocortin, pro-enkephalin or pro-dynorphin
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Abstract
本发明涉及黑皮质素治疗胰岛素敏感的应用。具体而言，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。
Description
本申请为2008年11月5日提交的、发明名称为“黑皮质素治疗胰岛素敏感的应用”的PCT申请PCT/US2008/012490的分案申请，所述PCT申请进入中国国家阶段的日期为2010年7月2日，申请号200880123893.1。
技术领域
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。
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(POMC;131个氨基酸长)的翻译后加工形成。POMC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,RecentProg.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,RecentProg.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,RecentProg.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,BrainRes.,809:302-306(1998);Farooqi等人,NEJMed.,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,.TransgenicRes.,9:145-54,(2000);Marsh等人,NatGenet.,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。
发明内容
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WO2007/008704国际专利申请，此处整体引用作为参考):
(R2R3)-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-R1(I)
其中:
A1是Acc、HN-(CH2)m-C(O)、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、Ala、β-Ala、Gaba、Aib、D-氨基酸或缺失;
A4是His、2-Pal、3-Pal、4-Pal、Taz、2-Thi、3-Thi或(X1,X2,X3,X4,X5)Phe;
A5是D-Phe、D-1-Nal、D-2-Nal、D-Trp、D-Bal、D-(X1,X2,X3,X4,X5)Phe、L-Phe或D-(Et)Tyr;
A6是Arg、hArg、Dab、Dap、Lys、Orn或HN-CH((CH2)n-N(R4R5))-C(O);
A7是Trp、1-Nal、2-Nal、Bal、Bip、D-Trp、D-1-Nal、D-2-Nal、D-Bal或D-Bip;
A8是Gly、D-Ala、Acc、Ala、β-Ala、Gaba、Apn、Ahx、Aha、HN-(CH2)s-C(O)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(O)、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、(C1-C30)烷基、(C1-C30)杂烷基、(C1-C30)酰基、(C2-C30)烯基、(C2-C30)炔基、芳基(C1-C30)烷基、芳基(C1-C30)酰基、被取代的(C1-C30)烷基、被取代的(C1-C30)杂烷基、被取代的(C1-C30)酰基、被取代的(C2-C30)烯基、被取代的(C2-C30)炔基、被取代的芳基(C1-C30)烷基、和被取代的芳基(C1-C30)酰基;
R4和R5各自在每种情况下独立地是H、(C1-C40)烷基、(C1-C40)杂烷基、(C1-C40)酰基、(C2-C40)烯基、(C2-C40)炔基、芳基(C1-C40)烷基、芳基(C1-C40)酰基、被取代的(C1-C40)烷基、被取代的(C1-C40)杂烷基、被取代的(C1-C40)酰基、被取代的(C2-C40)烯基、被取代的(C2-C40)炔基、被取代的芳基(C1-C40)烷基、被取代的芳基(C1-C40)酰基、(C1-C40)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;
X1、X2、X3、X4和X5各自在每种情况下独立地是H、F、Cl、Br、I、(C1-10)烷基、被取代的(C1-10)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、NO2或CN;
条件是
(I).当R4是(C1-C40)酰基、芳基(C1-C40)酰基、被取代的(C1-C40)酰基、被取代的芳基(C1-C40)酰基、(C1-C40)烷基磺酰基或-C(NH)-NH2时，那么R5是H或(C1-C40)烷基、(C1-C40)杂烷基、(C2-C40)烯基、(C2-C40)炔基、芳基(C1-C40)烷基、被取代的(C1-C40)烷基、被取代的(C1-C40)杂烷基、被取代的(C2-C40)烯基、被取代的(C2-C40)炔基或被取代的芳基(C1-C40)烷基;
(II).当R2为(C1-C30)酰基、芳基(C1-C30)酰基、被取代的(C1-C30)酰基、或被取代的芳基(C1-C30)酰基时，则R3是H、(C1-C30)烷基、(C1-C30)杂烷基、(C2-C30)烯基、(C2-C30)炔基、芳基(C1-C30)烷基、被取代的(C1-C30)烷基、被取代的(C1-C30)杂烷基、被取代的(C2-C30)烯基、被取代的(C2-C30)炔基、或被取代的芳基(C1-C30)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、Ile、Leu、hLeu、Met、β-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、β-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D-Bal、D-1-Nal、D-2-Nal、D-Phe、D-Trp或D-(Et)Tyr;
A6是Arg或hArg;
A7是Bal、Bip、1-Nal、2-Nal、Trp、D-Trp;
A8是A6c、D-Ala、Aha、Ahx、Ala、β-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-β-Ala-Lys)-NH2;SEQIDNO:1
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-A6c-Lys)-NH2;SEQIDNO:1
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH2;SEQIDNO:2
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-NH2;SEQIDNO:3
D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:3
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH2;SEQIDNO:3
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2;SEQIDNO:2
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH2;SEQIDNO:4
Ac-A6c-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:5
Ac-D-2-Nal-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:6
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:6
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:6
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:7
Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:7
Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:7
Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:7
Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:7
Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:8
Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:8
Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:8
Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:8
Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:8
Ac-Nle-c(D-Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:8
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:9
Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:9
Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:9
Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:9
Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:9
Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:10
Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:10
Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:10
Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:10
Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:10
Ac-Oic-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-Nip-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-hPro-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-hLeu-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-D-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
正丁酰基-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:12
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-β-hMet-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-Gaba-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-Cha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2;SEQIDNO:13
Ac-hCha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2;SEQIDNO:13
Ac-Leu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2;SEQIDNO:13
Ac-hLeu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2;SEQIDNO:13
Ac-Phe-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2;SEQIDNO:13
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-D-Ala-Lys)-NH2;SEQIDNO:14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-β-Ala-Lys)-NH2;SEQIDNO:14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Gaba-Lys)-NH2;SEQIDNO:14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Aha-Lys)-NH2;SEQIDNO:14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Apn-Lys)-NH2;SEQIDNO:14
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-NH2;SEQIDNO:15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-NH2;SEQIDNO:15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-NH2;SEQIDNO:15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-NH2;SEQIDNO:15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-NH2;SEQIDNO:15
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2;SEQIDNO:16
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-NH2;SEQIDNO:16
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-NH2;SEQIDNO:16
正丁酰基-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2;SEQIDNO:17
正丁酰基-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:17
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2;SEQIDNO:18
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-1-Nal-Cys)-NH2;SEQIDNO:18
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Bal-Cys)-NH2;SEQIDNO:18
Ac-Nle-c(Cys-D-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:61
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-D-Ala-Lys)-NH2;SEQIDNO:19
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-NH2;SEQIDNO:20
Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:21
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2;SEQIDNO:22
Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2;SEQIDNO:22
D-Phe-c(Cys-His-D-Phe-hArg-Trp-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:23
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:24
D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:25
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:24
D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:26
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:26
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2;SEQIDNO:27
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH2;SEQIDNO:28
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH2;SEQIDNO:28
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH;SEQIDNO:29
Ac-Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:30
Ac-Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:30
Ac-Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:30
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:30
Ac-Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:30
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:30
Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:31
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2;SEQIDNO:32
Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2;SEQIDNO:32
Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:33
Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:33
Ac-Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:33
Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:33
Ac-Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:33
Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:33
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:34
Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:34
Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:35
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH;SEQIDNO:36
Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)-NH2;SEQIDNO:37
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH2;SEQIDNO:38
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-β-Ala-Lys)-NH2;SEQIDNO:38
Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:39
Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH2;SEQIDNO:39
Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:40
Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:40
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-OH;SEQIDNO:41
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-OH;SEQIDNO:42
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-OH;SEQIDNO:43
D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-OH;SEQIDNO:43
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-OH;SEQIDNO:43
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-OH;SEQIDNO:42
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-OH;SEQIDNO:41
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH;SEQIDNO:44
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH;SEQIDNO:44
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH;SEQIDNO:29
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH;SEQIDNO:44
Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH;SEQIDNO:44
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH;SEQIDNO:44
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH;SEQIDNO:44
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH;SEQIDNO:44
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-OH;SEQIDNO:45
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-OH;SEQIDNO:45
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-OH;SEQIDNO:45
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-OH;SEQIDNO:45
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-OH;SEQIDNO:46
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-OH;SEQIDNO:46
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-OH;SEQIDNO:46
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-OH;SEQIDNO:46
Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH;SEQIDNO:47
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH;SEQIDNO:29
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-OH;SEQIDNO:48
Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2;SEQIDNO:49
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:50
Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:50
Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2;SEQIDNO:51
Ac-D-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2;SEQIDNO:52
Ac-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2;SEQIDNO:52
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2;SEQIDNO:51
Ac-D-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2;SEQIDNO:53
Ac-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2;SEQIDNO:53
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:7
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:24
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2;SEQIDNO:27
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2;SEQIDNO:32
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:34
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-NH2;SEQIDNO:1
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH2;SEQIDNO:2
D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:3
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH2;SEQIDNO:3
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2;SEQIDNO:2
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH2;SEQIDNO:4
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:6
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:6
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-NH2;SEQIDNO:15
Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:21
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2;SEQIDNO:22
D-Phe-c(Cys-His-D-Phe-hArg-Trp-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:23
D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:25
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:24
D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:26
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:26
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH2;SEQIDNO:28
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH2;SEQIDNO:28
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH;SEQIDNO:29
Ac-Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:30
Ac-Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:30
Ac-Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:30
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:30
Ac-Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:30
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:30
Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:31
Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2;SEQIDNO:32
Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:33
Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:33
Ac-Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:33
Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:33
Ac-Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:33
Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:33
Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:34
Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:35
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH;SEQIDNO:36
Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)-NH2;SEQIDNO:37
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2;SEQIDNO:16
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-NH2;SEQIDNO:16
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-NH2;SEQIDNO:20
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH2;SEQIDNO:38
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-β-Ala-Lys)-NH2;SEQIDNO:38
Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:39
Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH2;SEQIDNO:39
Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:40
Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:40或
Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2;SEQIDNO: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WO2007/008704国际专利申请，此处整体引用作为参考):
(R2R3)-A1-c(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、β-Ala、Gaba或Apn;
A9是Cys或Lys;
R2和R3各自独立地选自H或(C1-C6)酰基;
条件是
(I).当R2是(C1-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;SEQIDNO:54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Ala-Cys)-NH2;SEQIDNO:54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-β-Ala-Cys)-NH2;SEQIDNO:54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Apn-Cys)-NH2;SEQIDNO:54
Ac-c(Cys-Glu-His-D-Phe-Arg-Trp-Ala-Cys)-NH2;SEQIDNO:55
Ac-c(Cys-Glu-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2;SEQIDNO:55
Ac-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH2;SEQIDNO:56
Ac-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2;SEQIDNO:56
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH2;SEQIDNO:57
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-β-Ala-Cys)-NH2;SEQIDNO:57
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:57
或
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Ala-Lys)-NH2;SEQIDNO: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WO2007/008684国际专利申请，此处整体引用作为参考):
(R2R3)-B1-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-A11-A12-A13-B2-B3-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(O)、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、β-Ala、Gaba、Aib、D-氨基酸或缺失;
A4是His、2-Pal、3-Pal、4-Pal、Taz、2-Thi、3-Thi或(X1,X2,X3,X4,X5)Phe;
A5是D-Phe、D-1-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(O);
A7是Trp、1-Nal、2-Nal、Bal、Bip、Dip、Bpa、D-Trp、D-1-Nal、D-2-Nal、D-Bal、D-Bip、D-Dip或D-Bpa;
A8是Gly、D-Ala、Acc、Ala、β-Ala、Gaba、Apn、Ahx、Aha、HN-(CH2)s-C(O)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(O)、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-OH或-NH2;
R2和R3各自在每种情况下独立地选自H、(C1-C30)烷基、(C1-C30)杂烷基、(C1-C30)酰基、(C2-C30)烯基、(C2-C30)炔基、芳基(C1-C30)烷基、芳基(C1-C30)酰基、被取代的(C1-C30)烷基、被取代的(C1-C30)杂烷基、被取代的(C1-C30)酰基、被取代的(C2-C30)烯基、被取代的(C2-C30)炔基、被取代的芳基(C1-C30)烷基、和被取代的芳基(C1-C30)酰基;
R4和R5各自在每种情况下独立地是H、(C1-C40)烷基、(C1-C40)杂烷基、(C1-C40)酰基、(C2-C40)烯基、(C2-C40)炔基、芳基(C1-C40)烷基、芳基(C1-C40)酰基、被取代的(C1-C40)烷基、被取代的(C1-C40)杂烷基、被取代的(C1-C40)酰基、被取代的(C2-C40)烯基、被取代的(C2-C40)炔基、被取代的芳基(C1-C40)烷基、被取代的芳基(C1-C40)酰基、(C1-C40)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;
X1、X2、X3、X4和X5各自在每种情况下独立地是H、F、Cl、Br、I、(C1-10)烷基、被取代的(C1-10)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、NO2或CN;
条件是
(I).当R4是(C1-C40)酰基、芳基(C1-C40)酰基、被取代的(C1-C40)酰基、被取代的芳基(C1-C40)酰基、(C1-C40)烷基磺酰基或-C(NH)-NH2时，则R5是H、(C1-C40)烷基、(C1-C40)杂烷基、(C2-C40)烯基、(C2-C40)炔基、芳基(C1-C40)烷基、被取代的(C1-C40)烷基、被取代的(C1-C40)杂烷基、被取代的(C2-C40)烯基、被取代的(C2-C40)炔基或被取代的芳基(C1-C40)烷基;
(II).当R2为(C1-C30)酰基、芳基(C1-C30)酰基、被取代的(C1-C30)酰基、或被取代的芳基(C1-C30)酰基时，则R3是H、(C1-C30)烷基、(C1-C30)杂烷基、(C2-C30)烯基、(C2-C30)炔基、芳基(C1-C30)烷基、被取代的(C1-C30)烷基、被取代的(C1-C30)杂烷基、被取代的(C2-C30)烯基、被取代的(C2-C30)炔基、或被取代的芳基(C1-C30)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-Gln-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-Lys-Gln-Lys-(Arg)5、Arg-(Lys)2-Arg-Gln-(Arg)4、Arg-(Lys)2-(Arg)3-Gln-(Arg)2、Arg-(Lys)2-(Arg)4-Gln-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、Gln-(Arg)8、Gln-(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β-Ala、β-Ala-Gly、β-Ala-Tyr、β-Ala-Tyr-Gly、(β-Ala)2、(β-Ala)2-Gly、(β-Ala)2-Tyr、(β-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-Lys-Gln-Lys-(Arg)5、Arg-Lys-(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-Gln-(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)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、Gln-(Arg)8、Gln-(Arg)9或缺失;
A1是A6c、Cha、hCha、Chg、D-Chg、hChg、Gaba、hLeu、Met、β-hMet、D-2-Nal、Nip、Nle、Oic、Phe、D-Phe、hPhe、hPro或缺失;
A2是Cys
A3是D-Abu、Aib、Ala、β-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-Bal、D-1-Nal、D-2-Nal、D-Phe、D-(X1,X2,X3,X4,X5)Phe、D-Trp或D-(Et)Tyr;
A6是Arg或hArg;
A7是Bal、Bip、1-Nal、2-Nal、Trp或D-Trp;
A8是A5c、A6c、Aha、Ahx、Ala、β-Ala、Apn、Gaba、Gly或缺失;
A9是Cys、D-Cys、hCys、D-hCys、Lys、Pen或D-Pen;
A10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;(SEQIDNO:60)
Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-Doc-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH2;(SEQIDNO:61)
Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:62)
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:62)
Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:63)
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pro)2-Lys-Asp-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO:68)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO:73)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:74)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-Arg-Gln-(Arg)4-NH2;(SEQIDNO:75)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-Gln-(Arg)5-NH2;(SEQIDNO:76)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Gln-Lys-(Arg)5-NH2;(SEQIDNO:77)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)4-Gln-Arg-NH2;(SEQIDNO:78)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Aib-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:79)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:80)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:80)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2;(SEQIDNO:81)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:82)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:82)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO:83)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)3-Gln-(Arg)2-NH2;(SEQIDNO:85)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Gln-(Lys)2-(Arg)5-NH2;(SEQIDNO:86)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)5-Gln-NH2;(SEQIDNO:87)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:71)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:71)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:88)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO:89)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:88)
Ac-c(Cys-Glu-His-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;(SEQIDNO:90)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO:92)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:93)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO:94)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:95)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO:96)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:97)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO:92)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:98)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO:99)
Ac-c(Cys-Glu-His-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;(SEQIDNO:100)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO:101)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:102)
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;(SEQIDNO:103)
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;(SEQIDNO:104)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO:105)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:100)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO:102)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO:103)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-Arg-Gln-(Arg)4-NH2;(SEQIDNO:106)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-Gln-(Arg)5-NH2;(SEQIDNO:107)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Gln-Lys-(Arg)5-NH2;(SEQIDNO:108)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Gln-(Lys)2-(Arg)5-NH2;(SEQIDNO:109)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)3-Gln-(Arg)2-NH2;(SEQIDNO:110)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)4-Gln-Arg-NH2;(SEQIDNO:111)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)5-Gln-NH2;(SEQIDNO:112)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:113)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:113)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:114)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:114)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:115)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:115)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:116)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:116)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:117)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:117)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:118)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:118)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2;(SEQIDNO:119)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2;(SEQIDNO:119)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:120)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:120)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:121)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:121)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2;(SEQIDNO:122)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2;(SEQIDNO:122)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:123)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:123)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2;(SEQIDNO:124)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2;(SEQIDNO:124)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:125)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO: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-NH2;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO:128)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:129)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:129)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO: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;(SEQIDNO:130)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO:132)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:133)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:133)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:134)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:134)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2;(SEQIDNO:135)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO:136)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-(Lys)2-Arg-Gln-(Arg)4-NH2;(SEQIDNO: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;(SEQIDNO:136)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:138)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:138)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:138)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:139)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO:141)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO:142)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:143)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO:144)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-(Lys)2-Arg-Gln-(Arg)4-NH2;(SEQIDNO: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;(SEQIDNO:146)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:148)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:147)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:147)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:148)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:149)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:149)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:151)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:150)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:150)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:151)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:152)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:152)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:154)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:153)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:153)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:154)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:155)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:155)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:157)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:156)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:156)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:157)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:158)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:158)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:159)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:160)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:161)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:162)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:164)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:163)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:163)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:164)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:165)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:165)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:166)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:166)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:168)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:167)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:167)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:168)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:170)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:169)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:169)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:170)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:171)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:171)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:173)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:172)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:172)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:173)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:174)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:174)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:175)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:176)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:177)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO:179)
D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:180)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:181)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:182)
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:183)
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:184)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:183)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:185)
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:186)
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:185)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:186)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:188)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:187)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:188)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:189)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:190)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:189)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:190)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:191)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:192)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:191)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:192)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:193)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:194)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:193)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:194)
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:195)
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:196)
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:197)
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:198)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:199)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:200)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:199)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:200)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:201)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:202)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:203)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:203)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:205)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:204)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:204)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:205)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:207)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:206)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:206)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:207)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:208)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO:209)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:210)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:209)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:211)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:212)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:213)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:213)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:267)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:214)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:216)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:214)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO: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;(SEQIDNO:215)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:216)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:215)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:217)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:218)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:219)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO:221)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO:222)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:223)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO:224)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO: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;(SEQIDNO:224)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:225)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO:226)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:228)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO:230)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO:231)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:232)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:233)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:234)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:235)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:236)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:235)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:236)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:237)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:238)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:237)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:238)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:239)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:240)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:239)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:240)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:241)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:242)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:241)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:242)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:243)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:244)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:243)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:244)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:245)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:246)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:245)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:246)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:247)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:248)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:247)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:248)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:249)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:250)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:249)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:250)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:251)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:252)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:251)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:252)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:253)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:254)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:253)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:254)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:255)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:256)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:255)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:256)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:257)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:258)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:257)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:258)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:259)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:260)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:259)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:260)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:261)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:262)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:261)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:262)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:263)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:264)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:263)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:264)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:265)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:266)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:265)或
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO: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-His-A1-Arg-A2-A3-Cys)-(Pro)2-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、1-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-His-D-4-Br-Phe-Arg-Trp-Gly-Cys)-(Pro)2-Lys-Asp-NH2;(SEQIDNO:268)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-NH2;(SEQIDNO:269)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-NH2;(SEQIDNO:269)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-NH2;(SEQIDNO:269)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-NH2;(SEQIDNO:2690)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-β-Ala-Cys)-(Pro)2-Lys-Asp-NH2;(SEQIDNO:270)或
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Aib-Cys)-(Pro)2-Lys-Asp-NH2;(SEQIDNO: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(O)-NR8-(CH2)r-和-(CH2)r-NR8-C(O)-(CH2)t-;
R1和R2各自独立地是H、(C1-C10)烷基或被取代的(C1-C10)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-C10)烷基;
X1是
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-1-Nal、D-2-Nal、D-Phe或D-(X1,X2,X3,X4,X5)Phe;
A3是Arg、hArg、Dab、Dap、Lys或Orn;
A4是Bal、1-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-C10)烷基、被取代的(C1-C10)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-C10)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:
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)的前面种类的化合物的代表性实施方案如下:
c[乙内酰脲(C(O)-(Cys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:271)
c[乙内酰脲(C(O)-(hCys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:271)
c[乙内酰脲(C(O)-(Cys-D-Ala))-His-D-2-Nal-Arg-Trp-Cys]-NH2;(SEQIDNO:272)或
c[乙内酰脲(C(O)-(hCys-D-Ala))-His-D-2-Nal-Arg-Trp-Cys]-NH2;(SEQIDNO:272)
c[乙内酰脲(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Lys]-NH2;(SEQIDNO:273)
c[乙内酰脲(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH2;(SEQIDNO:273)
c[乙内酰脲(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH2;(SEQIDNO:273)或
c[乙内酰脲(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH2;(SEQIDNO:273)
c[乙内酰脲(C(O)-(Asp-His))-D-2-Nal-Arg-Trp-Lys]-NH2;(SEQIDNO:275)
c[乙内酰脲(C(O)-(Asp-His))-D-Phe-Arg-Trp-Lys]-NH2(SEQIDNO:274)
c[乙内酰脲(C(O)-(Asp-A3c))-D-Phe-Arg-Trp-Lys]-NH2;(SEQIDNO:274)
c[乙内酰脲(C(O)-(Asp-A5c))-D-Phe-Arg-Trp-Lys]-NH2;(SEQIDNO:274)
c[乙内酰脲(C(O)-(Asp-A6c))-D-Phe-Arg-Trp-Lys]-NH2;(SEQIDNO:274)
c[乙内酰脲(C(O)-(Asp-A3c))-D-2-Nal-Arg-Trp-Lys]-NH2;(SEQIDNO:275)
c[乙内酰脲(C(O)-(Asp-A5c))-D-2-Nal-Arg-Trp-Lys]-NH2;(SEQIDNO:275)
c[乙内酰脲(C(O)-(Asp-A6c))-D-2-Nal-Arg-Trp-Lys]-NH2;(SEQIDNO:275)
c[乙内酰脲(C(O)-(Asp-Aic))-D-Phe-Arg-Trp-Lys]-NH2;(SEQIDNO:274)
c[乙内酰脲(C(O)-(Asp-Apc))-D-Phe-Arg-Trp-Lys]-NH2;(SEQIDNO:274)
c[乙内酰脲(C(O)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NH2;(SEQIDNO:275)
c[乙内酰脲(C(O)-(Asp-Apc))-D-2-Nal-Arg-Trp-Lys]-NH2;(SEQIDNO:275)
c[乙内酰脲-(C(O)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NH2(SEQIDNO:275)
c[乙内酰脲-(C(O)-(Asp-Apc))-D-2-Nal-Arg-Trp-Lys]-NH2(SEQIDNO:275)
c[乙内酰脲(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH2;(SEQIDNO:276)
c[乙内酰脲(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH2;(SEQIDNO:276)或
c[乙内酰脲(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH2,(SEQIDNO:276)
c[乙内酰脲(C(O)-(Glu-His))-D-Phe-Arg-Trp-Dap]-NH2(SEQIDNO:277)
根据第六实施方案，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通式(VI)的黑皮质素受体化合物，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):
(VI)
其中
X1是
X2是
A1是Asp、Cys、D-Cys、Dab、Dap、Glu、Lys、Orn,Pen或D-Pen;
A2是L-或D-氨基酸;
A3是His、2-Pal、3-Pal、4-Pal、(X1,X2,X3,X4,X5)Phe、Taz、2-Thi或3-Thi;
A4是D-Bal、D-1-Nal、D-2-Nal、D-Phe或D-(X1,X2,X3,X4,X5)Phe;
A5是Arg、hArg、Dab、Dap、Lys或Orn;
A6是Bal、1-Nal、2-Nal、(X1,X2,X3,X4,X5)Phe或Trp、;
A7是Asp、Cys、D-Cys、Dab、Dap、Glu、Lys、Orn、Pen或D-Pen;
R1是H、(C1-C10)烷基或被取代的(C1-C10)烷基;
R2和R3各自独立地是H、(C1-C10)烷基、(C1-C10)杂烷基、芳基(C1-C5)烷基、被取代的(C1-C10)烷基、被取代的(C1-C10)杂烷基或被取代的芳基(C1-C5)烷基或R2和R3可融合在一起形成环部分;
R4是CO2H或C(O)NH2;
R5和R6各自独立地是H、(C1-C10)烷基、(C1-C10)杂烷基、芳基(C1-C5)烷基、被取代的(C1-C10)烷基、被取代的(C1-C10)杂烷基或被取代的芳基(C1-C5)烷基或R5和R6可融合在一起形成环部分;
R7和R8各自独立地是H、(C1-C10)烷基、(C1-C10)杂烷基、芳基(C1-C5)烷基、被取代的(C1-C10)烷基、被取代的(C1-C10)杂烷基或被取代的芳基(C1-C5)烷基;或R7和R8可融合在一起形成环部分;
R9是H、(C1-C10)烷基或被取代的(C1-C10)烷基;
n在其每种情况下独立地是1、2、3、4、5、6或7;
或其可药用盐。
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)的根据通式(VI)的优选种类的化合物是那些化合物其中：
A1是Cys;
A2是D-Ala、Asn、Asp、Gln、Glu或D-Phe;
A3是His;
A4是D-2-Nal或D-Phe;
A5是Arg;
A6是Trp;
A7是Cys或Pen;
R1、R2、R3和R9各自独立地是H;
R4是C(O)NH2;
R5和R6各自独立地是H、(C1-C10)烷基、(C1-C10)杂烷基、被取代的(C1-C10)烷基或被取代的(C1-C10)杂烷基或R5和R6可融合在一起形成环部分;
R7和R8各自独立地是H、(C1-C10)烷基、(C1-C10)杂烷基、被取代的(C1-C10)烷基或被取代的(C1-C10)杂烷基;
或其可药用盐。
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（通式(VI)）的优选的化合物包括:
乙内酰脲(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:278)
乙内酰脲(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:278)
乙内酰脲(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:278)
乙内酰脲(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2;(SEQIDNO:280)
乙内酰脲(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2;(SEQIDNO:280)
乙内酰脲(C(O)-(Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(D-Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Aib-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Val-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Ile-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Leu-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2;(SEQIDNO:281)
乙内酰脲(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2;(SEQIDNO:281)
乙内酰脲(C(O)-(D-Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:278)
乙内酰脲(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:278)
乙内酰脲(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2;(SEQIDNO:282)
乙内酰脲(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2;(SEQIDNO:282)
乙内酰脲(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:278)
乙内酰脲(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:278)
乙内酰脲(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2;(SEQIDNO:280)
乙内酰脲(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2;(SEQIDNO:280)
乙内酰脲(C(O)-(Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(D-Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Aib-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Val-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Ile-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Leu-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(D-Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:278)
乙内酰脲(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:278)
乙内酰脲(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)或
乙内酰脲(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Ala-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:283)
乙内酰脲(C(O)-(Val-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:283)
乙内酰脲(C(O)-(Gly-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:283)
乙内酰脲(C(O)-(A6c-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:284)
乙内酰脲(C(O)-(Gly-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:284)
乙内酰脲(C(O)-(Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:284)
乙内酰脲(C(O)-(D-Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:284)
乙内酰脲(C(O)-(Val-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:284)
乙内酰脲(C(O)-(Leu-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:284)
乙内酰脲(C(O)-(Cha-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:284)或
乙内酰脲(C(O)-(Aib-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:284)
乙内酰脲(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:285)
乙内酰脲(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2;(SEQIDNO:285)
乙内酰脲(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:286)
乙内酰脲(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2;(SEQIDNO:286)
乙内酰脲(C(O)-(Gly-D-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:287)
乙内酰脲(C(O)-(Gly-D-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:287)
乙内酰脲(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:288)和
乙内酰脲(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2;(SEQIDNO:288)
乙内酰脲(C(O)-(Nle-Ala))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2(SEQIDNO:289);
或其可药用盐。
在第七实施方案中，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属于环肽类似物种类的黑皮质素受体配体，该环肽类似物是具有如下描述的根据通式(VII)的结构的黑皮质素受体配体(见申请号为PCT/US08/06675国际专利申请，此处整体引用作为参考):
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(O)-NR8-(CH2)r-和-(CH2)r-NR8-C(O)-(CH2)t-;
R1和R5各自独立地是H、(C1-C10)烷基或被取代的(C1-C10)烷基;
R2和R3各自独立地是H、(C1-C10)烷基、(C1-C10)杂烷基、芳基(C1-C5)烷基、被取代的(C1-C10)烷基、被取代的(C1-C10)杂烷基或被取代的芳基(C1-C5)烷基或R2和R3可融合在一起形成环;
R4是OH或NH2;
R6和R7各自独立地是H、(C1-C10)烷基或被取代的(C1-C10)烷基;
A1是L-或D-氨基酸或缺失;
A2是His、2-Pal、3-Pal、4-Pal、(X1,X2,X3,X4,X5)Phe、Taz、2-Thi或3-Thi;
A3是D-Bal、D-1-Nal、D-2-Nal、D-Phe或D-(X1,X2,X3,X4,X5)Phe;
A4是Arg、hArg、Dab、Dap、Lys或Orn,;
A5是Bal、1-Nal、2-Nal、(X1,X2,X3,X4,X5)Phe或Trp,;
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;
或其可药用盐。
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)的根据通式(VII)的化合物的优选方面中，
A1是Ala、D-Ala、Asn、Asp、Gln、Glu或Gly;
或其可药用盐。
用于治疗哺乳动物受试者中胰岛素抵抗的根据通式(VII)的优选化合物包括下述化合物:
c[乙内酰脲(C(O)-(Nle-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(Ala-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(D-Ala-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(Aib-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(Val-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(Abu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(Leu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(Ile-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(Cha-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(A6c-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(Phe-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(Gly-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)或
c[乙内酰脲(C(O)-(Gly-Cys))-Glu-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:291)或
c[乙内酰脲(C(O)-(Gly-Cys))-Glu-His-D-Phe-Arg-Trp-Cys]-NH2(SEQIDNO:291);
或其可药用盐。
在第八实施方案中，本发明涉及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(VIII)的黑皮质素受体配体(见申请号为PCT/US08/07411国际专利申请，此处整体引用作为参考):
(R2R3)-A0-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-R1(VIII)
其中：
A0是芳香族的氨基酸
A1是Acc、HN-(CH2)m-C(O)、L-或D-氨基酸;
A2是Asp、Cys、D-Cys、hCys、D-hCys、Glu、Pen或D-Pen;
A3是Aib、Ala、β-Ala、Gaba、Gly或D-氨基酸;
A4是His、2-Pal、3-Pal、4-Pal、(X1,X2,X3,X4,X5)Phe、Taz、2-Thi或3-Thi;
A5是D-Bal、D-1-Nal、D-2-Nal、D-Phe、L-Phe、D-(X1,X2,X3,X4,X5)Phe、L-Phe、D-Trp或D-(Et)Tyr;
A6是Arg、hArg、Dab、Dap、Lys、Orn或HN-CH((CH2)n-N(R4R5))-C(O);
A7是Bal、D-Bal、Bip、D-Bip、1-Nal、D-1-Nal、2-Nal、D-2-Nal或D-Trp;
A8是Acc、Aha、Ahx、Ala、D-Ala、β-Ala、Apn、Gaba、Gly、HN-(CH2)s-C(O)或缺失;
A9是Cys、D-Cys、hCys、D-hCys、Dab、Dap、Lys、Orn、Pen或D-Pen;
A10是Acc、HN-(CH2)t-C(O)、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、(C1-C30)烷基、(C1-C30)杂烷基、(C1-C30)酰基、(C2-C30)烯基、(C2-C30)炔基、芳基(C1-C30)烷基、芳基(C1-C30)酰基、被取代的(C1-C30)烷基、被取代的(C1-C30)杂烷基、被取代的(C1-C30)酰基、被取代的(C2-C30)烯基、被取代的(C2-C30)炔基、被取代的芳基(C1-C30)烷基和被取代的芳基(C1-C30)酰基;
R4和R5各自在每种情况下独立地是H、(C1-C40)烷基、(C1-C40)杂烷基、(C1-C40)酰基、(C2-C40)烯基、(C2-C40)炔基、芳基(C1-C40)烷基、芳基(C1-C40)酰基、被取代的(C1-C40)烷基、被取代的(C1-C40)杂烷基、被取代的(C1-C40)酰基、被取代的(C2-C40)烯基、被取代的(C2-C40)炔基、被取代的芳基(C1-C40)烷基、被取代的芳基(C1-C40)酰基、(C1-C40)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;
X1、X2、X3、X4和X5各自在每种情况下独立地是H、F、Cl、Br、I、(C1-10)烷基、被取代的(C1-10)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、NO2或CN;
条件是
(I).当R4是(C1-C40)酰基、芳基(C1-C40)酰基、被取代的(C1-C40)酰基、被取代的芳基(C1-C40)酰基、(C1-C40)烷基磺酰基或-C(NH)-NH2时，那么R5是H或(C1-C40)烷基、(C1-C40)杂烷基、(C2-C40)烯基、(C2-C40)炔基、芳基(C1-C40)烷基、被取代的(C1-C40)烷基、被取代的(C1-C40)杂烷基、被取代的(C2-C40)烯基、被取代的(C2-C40)炔基或被取代的芳基(C1-C40)烷基;
(II).当R2是(C1-C30)酰基、芳基(C1-C30)酰基、被取代的(C1-C30)酰基或被取代的芳基(C1-C30)酰基时，那么R3是H、(C1-C30)烷基、(C1-C30)杂烷基、(C2-C30)烯基、(C2-C30)炔基、芳基(C1-C30)烷基、被取代的(C1-C30)烷基、被取代的(C1-C30)杂烷基、被取代的(C2-C30)烯基、被取代的(C2-C30)炔基或被取代的芳基(C1-C30)烷基;
(III).当A2是Cys、D-Cys、hCys、D-hCys、Pen或D-Pen时，那么A9是Cys、D-Cys、hCys、D-hCys、Pen或D-Pen;
(IV).当A2是Asp或Glu时，那么A9是Dab、Dap、Orn或Lys;
(V).当A8是Ala或Gly时，那么A1不是Nle;或
其可药用盐。
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一组化合物是其中
A0是1-Nal、2-Nal、His、Pff、Phe、Trp或Tyr;
A1是Arg;
A2是Cys;
A3是D-Ala;
A4是His;
A5是D-Phe;
A6是Arg;
A7是Trp;
A8缺失;
A9是Cys;
A10缺失;
或其可药用盐。
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)的前面组的化合物中优选的化合物具有下述通式:
Ac-Tyr-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:292)
Ac-2-Nal-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:292)
Ac-1-Nal-Arg-c(Cys-D-Ala-His-DPhe-Arg-Trp-Cys)-NH2;(SEQIDNO:292)
Ac-Phe-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:292)
Ac-Trp-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:292)
Ac-Pff-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:292)
H-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:293)或
Ac-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:292)
或其可药用盐。
在又一个优选实施方案中，如上述所限定的通式(I)、(II)、(III)、(IV)、(V)、(VI)、(VII)或(VIII)的一种或多种化合物，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)，或该化合物的可药用盐，以使用可药用载体或稀释剂的组合物形式提供给所述有需要的受试者。
在优选的实施方案中，本发明提供治疗有其需要的受试者之胰岛素抵抗的方法，包括外周施用有效量的黑皮质素受体4激动剂来治疗有其需要的受试者的胰岛素抵抗。
在一个方面，用于治疗有其需要的受试者的胰岛素抵抗（伴随或不伴随体重降低）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;SEQIDNO:1
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-A6c-Lys)-NH2;SEQIDNO:1
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-NH2;SEQIDNO:2
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-NH2;SEQIDNO:3
D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:3
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH2;SEQIDNO:3
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2;SEQIDNO:2
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-NH2;SEQIDNO:4
Ac-A6c-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:5
Ac-D-2-Nal-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:6
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:6
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:6
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:7
Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:7
Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:7
Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:7
Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:7
Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:8
Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:8
Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:8
Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:8
Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:8
Ac-Nle-c(D-Cys-Gly-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:8
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:9
Ac-Nle-c(Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:9
Ac-Nle-c(Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:9
Ac-Nle-c(Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:9
Ac-Nle-c(Cys-Gly-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:9
Ac-Nle-c(D-Cys-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:10
Ac-Nle-c(D-Cys-D-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:10
Ac-Nle-c(D-Cys-β-Ala-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:10
Ac-Nle-c(D-Cys-Gaba-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:10
Ac-Nle-c(D-Cys-Aib-His-D-Phe-Arg-Trp-D-Cys)-NH2;SEQIDNO:10
Ac-Oic-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-Nip-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-hPro-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-hLeu-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-D-Phe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
正丁酰基-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:12
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-β-hMet-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-Gaba-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:11
Ac-Cha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2;SEQIDNO:13
Ac-hCha-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2;SEQIDNO:13
Ac-Leu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2;SEQIDNO:13
Ac-hLeu-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2;SEQIDNO:13
Ac-Phe-c(Asp-His-D-Phe-Arg-D-Trp-Ala-Lys)-NH2;SEQIDNO:13
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-D-Ala-Lys)-NH2;SEQIDNO:14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-β-Ala-Lys)-NH2;SEQIDNO:14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Gaba-Lys)-NH2;SEQIDNO:14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Aha-Lys)-NH2;SEQIDNO:14
Ac-Nle-c(Asp-His-D-Phe-Arg-D-Trp-Apn-Lys)-NH2;SEQIDNO:14
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-NH2;SEQIDNO:15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-NH2;SEQIDNO:15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-NH2;SEQIDNO:15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-NH2;SEQIDNO:15
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-NH2;SEQIDNO:15
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2;SEQIDNO:16
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-NH2;SEQIDNO:16
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-NH2;SEQIDNO:16
正丁酰基-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2;SEQIDNO:17
正丁酰基-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:17
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Cys)-NH2;SEQIDNO:18
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-1-Nal-Cys)-NH2;SEQIDNO:18
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Bal-Cys)-NH2;SEQIDNO:18
Ac-Nle-c(Cys-D-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:61
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-D-Ala-Lys)-NH2;SEQIDNO:19
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-NH2;SEQIDNO:20
Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:21
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2;SEQIDNO:22
Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2;SEQIDNO:22
D-Phe-c(Cys-His-D-Phe-hArg-Trp-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:23
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:24
D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:25
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:24
D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:26
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-NH2;SEQIDNO:26
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-NH2;SEQIDNO:27
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Trp-Lys)-NH2;SEQIDNO:28
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Lys)-NH2;SEQIDNO:28
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-OH;SEQIDNO:29
Ac-Nle-c(Cys-D-Abu-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:30
Ac-Nle-c(Cys-D-Val-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:30
Ac-Nle-c(Cys-D-Ile-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:30
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:30
Ac-Nle-c(Cys-D-Tle-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:30
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:30
Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:31
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2;SEQIDNO:32
Ac-Nle-c(Pen-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2;SEQIDNO:32
Ac-Leu-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:33
Ac-Cha-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:33
Ac-Ile-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:33
Ac-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:33
Ac-Val-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:33
Ac-2-Nal-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:33
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:34
Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:34
Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:35
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH;SEQIDNO:36
Ac-Nle-c(Cys-His-Phe-Arg-D-Trp-Gaba-Cys)-NH2;SEQIDNO:37
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Ala-Lys)-NH2;SEQIDNO:38
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-β-Ala-Lys)-NH2;SEQIDNO:38
Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:39
Ac-Nle-c(Cys-His-D-2-Nal-Arg-Trp-Ahx-Cys)-NH2;SEQIDNO:39
Ac-hPhe-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:40
Ac-Cha-c(Asp-His-D-2-Nal-Arg-Trp-Gaba-Lys)-NH2;SEQIDNO:40
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-OH;SEQIDNO:41
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-OH;SEQIDNO:42
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Ala-D-Cys)-Thr-OH;SEQIDNO:43
D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-OH;SEQIDNO:43
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-OH;SEQIDNO:43
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-OH;SEQIDNO:42
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Apn-Lys)-OH;SEQIDNO:41
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH;SEQIDNO:44
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH;SEQIDNO:44
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH;SEQIDNO:44
Ac-D-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH;SEQIDNO:44
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH;SEQIDNO:44
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH;SEQIDNO:44
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-OH;SEQIDNO:44
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Gaba-Cys)-OH;SEQIDNO:45
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-OH;SEQIDNO:45
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-OH;SEQIDNO:45
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-D-Ala-Cys)-OH;SEQIDNO:45
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-OH;SEQIDNO:46
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-2-Nal-Cys)-OH;SEQIDNO:46
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-1-Nal-Cys)-OH;SEQIDNO:46
Ac-Nle-c(Cys-D-Ala-His-D-2-Nal-Arg-Bal-Cys)-OH;SEQIDNO:46
Ac-Nle-c(Pen-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH;SEQIDNO:47
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-OH;SEQIDNO:48
Ac-Arg-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2;SEQIDNO:49
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:50
Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;SEQIDNO:50
Ac-D-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2;SEQIDNO:51
Ac-D-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2;SEQIDNO:52
Ac-Arg-c(Cys-His-D-Phe-Arg-Trp-Gaba-Pen)-NH2;SEQIDNO:52
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2;SEQIDNO:51
Ac-D-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2;SEQIDNO:53
Ac-Arg-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-NH2;SEQIDNO:53
Ac-Nle-c(Cys-3-Pal-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:35
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-NH2;SEQIDNO:54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-D-Ala-Cys)-NH2;SEQIDNO:54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-β-Ala-Cys)-NH2;SEQIDNO:54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gaba-Cys)-NH2;SEQIDNO:54
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Apn-Cys)-NH2;SEQIDNO:54
Ac-c(Cys-Glu-His-D-Phe-Arg-Trp-Ala-Cys)-NH2;SEQIDNO:55
Ac-c(Cys-Glu-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2;SEQIDNO:55
Ac-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH2;SEQIDNO:56
Ac-c(Cys-D-Ala-His-D-Phe-Arg-2-Nal-Ala-Cys)-NH2;SEQIDNO:56
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Ala-Cys)-NH2;SEQIDNO:57
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-β-Ala-Cys)-NH2;SEQIDNO:57
Ac-Nle-c(Asp-D-Ala-His-D-Phe-Arg-Bal-Ala-Lys)-NH2;SEQIDNO:58
Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH2;(SEQIDNO:60)
Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-Doc-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-NH2;(SEQIDNO:61)
Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:62)
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:62)
Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:63)
Ac-Nle-c(Asp-His-D-2-Nal-Arg-Trp-Lys)-(Pro)2-Lys-Asp-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO66)
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;(SEQIDNO: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;(SEQIDNO:68)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO:73)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:74)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-Arg-Gln-(Arg)4-NH2;(SEQIDNO:75)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-Gln-(Arg)5-NH2;(SEQIDNO:76)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-Gln-Lys-(Arg)5-NH2;(SEQIDNO:77)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)4-Gln-Arg-NH2;(SEQIDNO:78)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Aib-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:79)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:80)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:80)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2;(SEQIDNO:81)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:82)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:82)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO:83)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)3-Gln-(Arg)2-NH2;(SEQIDNO:85)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Gln-(Lys)2-(Arg)5-NH2;(SEQIDNO:86)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)5-Gln-NH2;(SEQIDNO:87)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:71)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-(Lys)2-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:71)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:88)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO:89)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:88)
Ac-c(Cys-Glu-His-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;(SEQIDNO:90)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO:92)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:95)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO:96)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:97)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO:92)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:98)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO:99)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO:104)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO:105)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:100)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO:102)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO:103)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:113)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:113)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:114)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:114)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:115)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:115)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:116)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:116)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:118)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:118)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2;(SEQIDNO:119)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:120)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:120)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:121)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:121)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2;(SEQIDNO:122)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2;(SEQIDNO:122)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)6-Gln-(Arg)3-NH2;(SEQIDNO:124)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:125)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO: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-NH2;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO:130)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:133)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:134)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:134)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2;(SEQIDNO:135)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Arg-Asp-β-Ala-Tyr-Gly-(Arg)6-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO:136)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-Arg-(Lys)2-Arg-Gln-(Arg)4-NH2;(SEQIDNO: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;(SEQIDNO:136)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:138)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:138)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;_(SEQIDNO:139)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO:141)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Gly-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO:142)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)2-Lys-(Arg)2-Gln-(Arg)3-NH2;(SEQIDNO:143)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Arg-Lys-(Arg)3-Gln-(Arg)3-NH2;(SEQIDNO:144)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:148)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:148)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:149);
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:149)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:151)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:150)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:150)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:151)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:152)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:152)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:154)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;_(SEQIDNO:153)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:154)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:155)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:155)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:157)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:156)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:156)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:157)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:158)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:158)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:159)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:160)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:161)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Ala-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:162)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:164)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:163)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:163)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:164)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:165)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:165)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:166)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:166)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:168)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:167)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:167)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:168)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:170)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:169)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:169)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:170)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:171)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:171)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:173)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:172)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-Doc-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:172)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:173)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:174)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Lys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:174)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:175)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-β-Ala-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:176)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:177)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Ahx-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO:179)
D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:180)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:181)
Ac-Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:182)
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:183)
Ac-Cha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:184)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:183)
Ac-Nle-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:185)
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:186)
Ac-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:185)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:186)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:188)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:187)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:188)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:189)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:190)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:189)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:190)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:191)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:192)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:191)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:192)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;_(SEQIDNO:193)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-Doc-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:194)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:193)
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:194)
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:195)
Ac-D-Chg-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:196)
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:197)
Ac-hPhe-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:198)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:199)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:200)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;_(SEQIDNO:199)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-Ahx-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:200)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:201)
Ac-Nle-c(Cys-His-D-Phe-Arg-D-Trp-β-Ala-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:202)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;_(SEQIDNO:203)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:203)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:205)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:204)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:204)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:205)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;_(SEQIDNO:207)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:206)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:206)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:207)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:208)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO:209)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:210)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:209)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:211)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:212)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:213)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:213)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:267)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:214)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:216)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-Gly-(Arg)5-Gln-(Arg)3-NH2;_(SEQIDNO:214)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO: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;(SEQIDNO:215)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:216)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:215)
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:217)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:218)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:219)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO:221)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO:222)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:223)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO:224)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-Doc-(Arg)5-Gln-(Arg)4-NH2;_(SEQIDNO: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;(SEQIDNO:224)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-(Doc)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:225)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO:226)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:228)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO: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;(SEQIDNO:230)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-Doc-(Arg)5-Gln-(Arg)3-NH2;_(SEQIDNO: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;(SEQIDNO:231)
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:232)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:233)
Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Gly-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:234)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:235)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:236)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:235)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:236)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:237)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:238)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:237)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:238)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:239)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:240)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:239)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:240)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:241)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:242)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:241)
Nle-c(Cys-His-D-Phe-Arg-Trp-Apn-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:242)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:243)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:244)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:243)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:244)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;_(SEQIDNO:245)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:246)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:245)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:246)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:247)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:248)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:247)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:248)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;_(SEQIDNO:249)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:250)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:249)
Ac-Nle-c(Cys-D-Leu-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:250)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:251)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:252)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:251)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:252)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;_(SEQIDNO:253)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:254)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:253)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:254)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;_(SEQIDNO:255)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:256)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:255)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:256)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;_(SEQIDNO:257)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:258)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:257)
Ac-Nle-c(Cys-D-Cha-His-D-Phe-Arg-Trp-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:258)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:259)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:260)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:259)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:260)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:261)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-β-Ala-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:262)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:261)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(β-Ala)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:262)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:263)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:264)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:263)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-(Arg)5-Gln-(Arg)3-NH2;(SEQIDNO:264)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:265)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-Doc-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:266)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-Tyr-Gly-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:265)
Nle-c(Cys-His-D-Phe-Arg-Trp-Gaba-Cys)-(Doc)2-(Arg)5-Gln-(Arg)4-NH2;(SEQIDNO:266)
Ac-c(Cys-Glu-His-D-4-Br-Phe-Arg-Trp-Gly-Cys)-(Pro)2-Lys-Asp-NH2;(SEQIDNO:268)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Ala-Cys)-(Pro)2-Lys-Asp-NH2;(SEQIDNO:269)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Ala-Cys)-(Pro)2-Lys-Asp-NH2;(SEQIDNO:269)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-1-Nal-Ala-Cys)-(Pro)2-Lys-Asp-NH2;(SEQIDNO:269)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-Bal-Ala-Cys)-(Pro)2-Lys-Asp-NH2;(SEQIDNO:269)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-β-Ala-Cys)-(Pro)2-Lys-Asp-NH2;(SEQIDNO:270)
Ac-c(Cys-Glu-His-D-2-Nal-Arg-2-Nal-Aib-Cys)-(Pro)2-Lys-Asp-NH2;(SEQIDNO:270)
c[乙内酰脲(C(O)-(Cys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:271)
c[乙内酰脲(C(O)-(hCys-D-Ala))-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:271)
c[乙内酰脲(C(O)-(Cys-D-Ala))-His-D-2-Nal-Arg-Trp-Cys]-NH2;(SEQIDNO:272)
c[乙内酰脲(C(O)-(hCys-D-Ala))-His-D-2-Nal-Arg-Trp-Cys]-NH2;(SEQIDNO:272)
c[乙内酰脲(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Lys]-NH2;(SEQIDNO:273)
c[乙内酰脲(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH2;(SEQIDNO:273)
c[乙内酰脲(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH2;(SEQIDNO:273)
c[乙内酰脲(C(O)-(Asp-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH2;(SEQIDNO:273)
c[乙内酰脲(C(O)-(Asp-His))-D-2-Nal-Arg-Trp-Lys]-NH2;(SEQIDNO:275)
c[乙内酰脲(C(O)-(Asp-His))-D-Phe-Arg-Trp-Lys]-NH2;(SEQIDNO:274)
c[乙内酰脲(C(O)-(Asp-A3c))-D-Phe-Arg-Trp-Lys]-NH2;(SEQIDNO:274)
c[乙内酰脲(C(O)-(Asp-A5c))-D-Phe-Arg-Trp-Lys]-NH2;(SEQIDNO:274)
c[乙内酰脲(C(O)-(Asp-A6c))-D-Phe-Arg-Trp-Lys]-NH2;(SEQIDNO:274)
c[乙内酰脲(C(O)-(Asp-A3c))-D-2-Nal-Arg-Trp-Lys]-NH2;(SEQIDNO:275)
c[乙内酰脲(C(O)-(Asp-A5c))-D-2-Nal-Arg-Trp-Lys]-NH2;(SEQIDNO:275)
c[乙内酰脲(C(O)-(Asp-A6c))-D-2-Nal-Arg-Trp-Lys]-NH2;(SEQIDNO:275)
c[乙内酰脲(C(O)-(Asp-A5c))-D-2-Nal-Arg-Trp-Lys]-NH2;(SEQIDNO:275)
c[乙内酰脲(C(O)-(Asp-Aic))-D-Phe-Arg-Trp-Lys]-NH2;(SEQIDNO:274)
c[乙内酰脲(C(O)-(Asp-Apc))-D-Phe-Arg-Trp-Lys]-NH2;(SEQIDNO:274)
c[乙内酰脲(C(O)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NH2;(SEQIDNO:275)
c[乙内酰脲(C(O)-(Asp-Apc))-D-2-Nal-Arg-Trp-Lys]-NH2;(SEQIDNO:275)
c[乙内酰脲-(C(O)-(Asp-Aic))-D-2-Nal-Arg-Trp-Lys]-NH2;(SEQIDNO:275)
c[乙内酰脲-(C(O)-(Asp-Apc))-D-2-Nal-Arg-Trp-Lys]-NH2;(SEQIDNO:275)
c[乙内酰脲(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Orn]-NH2;(SEQIDNO:276)
c[乙内酰脲(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dab]-NH2;(SEQIDNO:276)
c[乙内酰脲(C(O)-(Glu-D-Ala))-His-D-Phe-Arg-Trp-Dap]-NH2;(SEQIDNO:276)
c[乙内酰脲(C(O)-(Glu-His))-D-Phe-Arg-Trp-Dap]-NH2;(SEQIDNO:277)
乙内酰脲(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:278)
乙内酰脲(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:278)
乙内酰脲(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:278)
乙内酰脲(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Nle-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2;(SEQIDNO:280)
乙内酰脲(C(O)-(Gly-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Pen)-NH2;(SEQIDNO:280)
乙内酰脲(C(O)-(Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(D-Ala-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Aib-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Val-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Ile-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Leu-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Gly-Gly))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2;(SEQIDNO:281)
乙内酰脲(C(O)-(Nle-Gly))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2;(SEQIDNO:281)
乙内酰脲(C(O)-(D-Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:278)
乙内酰脲(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:279)
乙内酰脲(C(O)-(D-Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2;(SEQIDNO:282)
乙内酰脲(C(O)-(Arg-Gly))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2;(SEQIDNO:282)
乙内酰脲(C(O)-(Ala-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:283)
乙内酰脲(C(O)-(Val-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:283)
乙内酰脲(C(O)-(Gly-Nle))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:283)
乙内酰脲(C(O)-(A6c-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:284)
乙内酰脲(C(O)-(Gly-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:284)
乙内酰脲(C(O)-(Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:284)
乙内酰脲(C(O)-(D-Ala-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:284)
乙内酰脲(C(O)-(Val-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:284)
乙内酰脲(C(O)-(Leu-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:284)
乙内酰脲(C(O)-(Cha-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:284)
乙内酰脲(C(O)-(Aib-Nle))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:284)
乙内酰脲(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:285)
乙内酰脲(C(O)-(Gly-Arg))-c(Cys-Glu-His-D-2-Nal-Arg-Trp-Cys)-NH2;(SEQIDNO:285)
乙内酰脲(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:286)
乙内酰脲(C(O)-(Gly-Arg))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2;(SEQIDNO:286)
乙内酰脲(C(O)-(Gly-D-Arg))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:287)
乙内酰脲(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:288)
乙内酰脲(C(O)-(Gly-D-Arg))-c(Cys-D-Ala-His-D-2-Nal-Arg-Trp-Cys)-NH2;(SEQIDNO:288)
乙内酰脲(C(O)-(Nle-Ala))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:289)
c[乙内酰脲(C(O)-(Ala-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2、(SEQIDNO:290)
c[乙内酰脲(C(O)-(Nle-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(D-Ala-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(Aib-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(Val-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(Abu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(Leu-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(Ile-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(Cha-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(A6c-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(Phe-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(Gly-Cys))-D-Ala-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:290)
c[乙内酰脲(C(O)-(Gly-Cys))-Glu-His-D-Phe-Arg-Trp-Cys]-NH2;(SEQIDNO:291)
Ac-Tyr-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:292)
Ac-2-Nal-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:292)
Ac-1-Nal-Arg-c(Cys-D-Ala-His-DPhe-Arg-Trp-Cys)-NH2;(SEQIDNO:292)
Ac-Phe-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:292)
Ac-Trp-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:292)
Ac-Pff-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:292)
H-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:293)和
Ac-His-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2;(SEQIDNO:292)
或其可药用盐。
在一个优选的方面，用于治疗有其需要的受试者的胰岛素抵抗的黑皮质素受体4激动剂是Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2(SEQIDNO:50)或其可药用盐。在另一个优选的方面，用于治疗有其需要的受试者的胰岛素抵抗的黑皮质素受体4激动剂是乙内酰脲(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2(SEQIDNO:278)或其可药用盐。
在本发明的其他方面，对用于治疗胰岛素抵抗的本发明之化合物或包含化合物的组合物或化合物的可药用盐的施用是连续的、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、每两月一次、或更长。
需要治疗的受试者可以是肥胖的、超重的、正常体重的或偏瘦的。肥胖、超重、正常体重或偏瘦的受试者可罹患II型糖尿病。对用于治疗胰岛素抵抗的本发明之化合物或包含化合物的组合物或化合物的可药用盐的优选施用是外周施用。外周施用的例子包括通过经口、皮下、腹膜内、肌内、静脉内、直肠、经皮、或鼻内形式的施用。
发明详述
最近的研究报道全世界超重的人的数目惊人，他们受到很多种严重和花费巨大的健康问题的困扰。根据世界卫生组织报道(Kouris-Blazos等人在AsiaPac.J.Clin.Nutr.,2007,16:329-338中所报道)，估计全世界有10亿人超重，他们之中估计有3亿人肥胖。估计有2千2百万年龄在5岁以下的儿童严重超重，仅在欧洲联盟内超重的儿童数目预计每年就增加130万个儿童(Kosti等人,2006,Cent.Eur.J.PublicHealth,14:151-159)。根据大都会人寿保险公司（MetropolitanLifeInsuranceCo.,）提供的统计公报(1959,40:1)的定义，肥胖症是人们超过正常体重的大约20-25%以上的状态。或者，如果具有风险因子的个人的体重指数大于正常的25%，或大于正常的30%，则个体被认为是肥胖的(见Bray等人,Diabetes/MetabolismReview,1988,4:653-679或Flynn等人,Proc.NutritionalSociety,1991,50:413)。肥胖症的一个主要原因是消费高热量的饮食(Riccardi等人,Clin.Nutr.,2004,23:447-456)。
糖尿病是困扰许多超重和肥胖人群的慢性消耗性疾病。据估计仅美国就有二千零八十万人患有糖尿病，还有另外六百万以上是处于未诊断的病例(Cornell,Manag.CarePharm.,2007,13:S11-5)。2型糖尿病(本文中也称作II型糖尿病)是慢性疾病，其特征是胰岛素抵抗、胰岛素分泌受损和高血糖。在世界范围内，据信II型糖尿病影响大约1.71亿人，引起数目众多的微血管和大血管并发症导致发病和死亡(Mudaliar,IndianJ.Med.Res.,2007,125:275-296)。Mudaliar还指出尽管可获得可用的抗高血糖试剂，许多病人中对葡萄糖仍然难以控制。
胰岛素抵抗（也称作胰岛素敏感度降低）是一种病症，其中清除受试者血液中葡萄糖所需的胰岛素的量与正常非胰岛素敏感的受试者血液中清除等量葡萄糖所需的胰岛素的量相比增加了。胰岛素抵抗被认为是肥胖症和II型糖尿病之间的主要联系(见Obici等人,J.Clin.Inv.,2001,108:1079-1085及其中的参考文献)。已知高脂饮食喂养的大鼠显示出体重的增加(饮食诱导肥胖症或DIO)，并且胰岛素敏感度降低。这种DIO大鼠提供了研究肥胖症导致的胰岛素抵抗机制的动物模型(参见，例如Banno等人,FEBSletters,2007,581:1131-1136)。在DIO大鼠中脂肪组织的大小和重量增加，人们认为伴随的脂肪细胞的肥大导致脂肪细胞因子（adipocytokine）（如已知调节胰岛素敏感度的瘦蛋白和脂连蛋白）释放的改变；人们认为脂肪组织的形态改变以及血浆脂肪细胞因子水平的改变是DIO大鼠中胰岛素抵抗的原因之一(总结在Banno,等人,FEBSletters,2007,581:1131-1136以及其中的参考文献中)。
人们提出黑皮质素在能量代谢和稳态中发挥巨大作用。黑皮质素从POMC前体剪切而来，通过结合位于脑中的黑皮质素受体家族成员发挥作用。脑中黑皮质素的主要作用是降低食物摄取，然而，也显示当不摄取食物或当食物摄取保持恒定时直接向脑室注射黑皮质素激动剂或拮抗剂影响外周胰岛素的作用(见Schwartz等人,Nature,2000,404:661-671;Seeley等人,Ann.Rev.Nutr.,2004,24:133-149;Cone等人,RecentProg.Horm.Res.,1996,51:287-317;Heijbor等人,Diabetologia,2005,48:1621-1626;Obici等人,J.Clin.Inv.,2001,108:1079-1085)。总之，这些数据提示中枢施用黑皮质素影响胰岛素敏感度，并且可不依赖于能量平衡而发挥这种作用。Banno等人,(FEBSletters,2007,581:1131-1136)证明向DIO大鼠脑内注射黑皮质素激动剂改善外周胰岛素敏感度，降低白脂肪组织中脂肪细胞的大小并增加其数目，并且降低肝中甘油三酯含量。
考虑到需要治疗的超重和/或胰岛素抵抗受试者的数量众多，脑内施用是不太可能的向患者给药的方式。因此，在本领域中需要鉴定适合通过外周施用的黑皮质素激动剂和拮抗剂来影响胰岛素作用和能量代谢的参数如胰岛素敏感度、白脂肪组织细胞特征、甘油三酯水平等等。
术语和缩写
如本文所用的，“肥胖的受试者”或哺乳动物的特征是对所述受试者来说具有比正常体重多大约20%或更多的体重。正常体重可通过比较该受试者在之前的时间点上（如当胰岛素代谢正常时）的体重，或通过比较该受试者的体重与其他相似年龄和/或状态的受试者之平均体重来确定。
如本文所用的，“超重的受试者”或哺乳动物的特征是对所述受试者来说具有比正常体重多大约5%至多大约20%的体重。正常体重可通过比较该受试者在之前的时间点上（如当胰岛素代谢正常时）的体重，或通过比较该受试者的体重与其他相似年龄和/或状态的受试者之平均体重来确定。
如本文所用的，“正常的受试者”或哺乳动物的特征是对所述受试者来说具有至多比正常体重多大约5%至大约少5%范围的体重。正常体重可通过比较该受试者在之前的时间点上（如当胰岛素代谢正常时）的体重，或通过比较该受试者的体重与其他相似年龄和/或状态的受试者之平均体重来确定。
如本文所用的，“偏瘦的受试者”或哺乳动物的特征是对所述受试者来说具有比正常体重低大约5%至30%或甚至50%的体重。正常体重可通过比较该受试者在之前的时间点上（如当胰岛素代谢正常时）的体重，或通过比较该受试者的体重与其他相似年龄和/或状态的受试者之平均体重来确定。
如本文所用的，术语“治疗（treat、treating和treatment）”包括姑息性、治愈性和预防性治疗。
如本文所用的，“可测量的”的意思是指生物效应既可重复又与该测定的基线变异性有显著差异。
如本文所用的，外周施用包括除了颅内施用之外的其他一切形式的施用本发明的化合物或包含化合物的组合物。外周施用的例子包括但不限于经口、肠胃外（例如，肌内、腹膜内、静脉内或皮下注射、植入等等）、经鼻、阴道、直肠、舌下或者局部施用途径施用，包括透皮贴剂应用等等。
如本文所用和本申请全文所用的，“受试者”是指哺乳动物或非哺乳动物包括，例如，但不限于，人类、大鼠、小鼠或农场动物。提及受试者并不必然表示疾病或病症的存在。术语“受试者”包括，例如作为实验一部分的给予黑皮质素类似物的哺乳动物或非哺乳动物，被治疗以帮助改善疾病或病症的哺乳动物或非哺乳动物，以及被预防性治疗以阻止或预防疾病或病症发生的哺乳动物或非哺乳动物。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。
本发明的化合物或组合物的“治疗可接受的量”，不论剂型或施用途径，是引起受试者中合乎需要的生物反应的量。在生物体内，治疗量的生物效应可发生在许多水平并可在许多水平测量。例如，治疗量的生物效应可发生在细胞水平，并可通过测量结合黑皮质素和/或黑皮质素类似物的受体的反应在细胞水平测量，或治疗量的生物效应可发生在全身水平并在全身水平进行测量，如导致胰岛素水平的升高/降低。治疗量的生物效应可发生在生物体水平并在生物体水平测量，如缓解受试者的疾病或状态的症状或进展。本发明的化合物或组合物的“治疗可接受的量”，不论剂型或施用途径，可导致受试者中一种或更多种生物反应。在本发明的化合物或组合物在体外系统中测试的情况下，化合物或组合物的治疗可接受的量可视为在选定体外系统中产生可测量的反应量。
用于定义肽的术语是通常用于本领域的术语，其中N-末端氨基出现在左边，C-末端羧基出现在右边。当氨基酸具有D和L异构形式时，除非明确指出相反，它是所代表氨基酸的L形式。
用于治疗胰岛素抵抗（伴随或不伴随体重减轻）的本发明的化合物可具有一个或更多个手性中心，因此存在许多立体异构形式。所有立体异构体及其混合物包含于本发明的范围中。外消旋化合物可通过制备HPLC和带有手性固定相的柱子分离，或者使用本领域技术人员已知的方法分解以产生单个对映体。此外，可分解手性中间化合物并用其制备本发明的手性化合物。
用于治疗胰岛素抵抗（伴随或不伴随体重减轻）的本发明的化合物可以一种或更多种互变异构形式存在。所有互变异构体及其混合物包含于本发明的范围中。例如要求保护2-羟基吡啶基也覆盖其互变异构形式，α-吡啶酮基。
除非另外定义，本文中使用的所有技术和科学术语具有与本发明所属领域普通技术人员通常理解的相同的含义。而且，本文提到的所有出版物、专利申请、专利和其他参考文献都整体引入本文作为参考。
本文中使用的某些其他缩写如下定义：
Boc:叔丁氧基羰基
Bzl:苯甲基
DCM:二氯甲烷
DIC:N,N-二异丙基碳二亚胺
DIEA:二异丙基乙胺
Dmab:4-{N-(1-(4,4-二甲基-2,6-二氧代环亚己基)-3-甲基丁基)-氨基}苯甲基
DMAP:4-(二甲基氨基)吡啶
DMF:二甲基甲酰胺
DNP:2,4-二硝基苯基
Fm:芴基甲基
Fmoc:芴基甲氧基羰基
FOR:甲酰基
HBTU:2-(1H-苯并三唑-1-基)-1,1,3,3-四甲基脲六氟磷酸盐
cHex:环己基
HOAT:O-(7-氮杂苯并三唑-1-基)-1,1,3,3-四甲基脲六氟磷酸盐
HOBt:1-羟基-苯并三唑
MBHA:4-甲基二苯甲基胺
Mmt:4-甲氧基三苯甲基
NMP:N-甲基吡咯烷酮
O-tBu:叔丁氧基
Pbf:2,2,4,6,7-五甲基二氢苯并呋喃-5-磺酰基
PyBroP:溴-三-吡咯烷-六氟磷酸盐
tBu:叔丁基
TIS:三异丙基硅烷
TOS:甲苯磺酰基
Trt:三苯甲基
TFA:三氟乙酸
TFFH:四甲基氟代脲六氟磷酸酯
Z:苄氧羰基
除非另外指出，除了N-末端氨基酸外，本公开中氨基酸的所有缩写（例如Ala）都代表-NH-C(R)(R')-CO-的结构，其中R和R’各自独立地为氢或者氨基酸的侧链（例如，对于丙氨酸，R=CH3且R'=H），或者R和R’可以结合形成环体系。
对于N-末端氨基酸，该缩写代表结构：
在例如Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2(SEQIDNO:7)中明示的“NH2”表示该肽的C-末端被酰胺化。Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)(SEQIDNO:36)或备选地Ac-Nle-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-OH(SEQIDNO:36)表示C-末端是游离酸。
“-c(Cys-Cys)-”或“-环(Cys-Cys)-”表示结构：
“-c(Cys-Pen)-”或“-环(Cys-Pen)-”表示结构：
“-c(Asp-Lys)-”或“-环(Asp-Lys)-”表示结构：
申请人设计了下述速记法用于命名具体实施方案和/或种类（species）：
“乙内酰脲C(O)-(Aa-Ab)”表示结构：
其中氨基酸“Aa”具有结构：以及
氨基酸“Ab”结构：
例如，“c[乙内酰脲(C(O)-(Cys-Ab))-A1-A2-A3-A4-Cys]-”表示的化合物将具有下述结构：
而“c[乙内酰脲(C(O)-(Ab-Cys))-A1-A2-A3-A4-Cys]-”表示的化合物将具有结构：
作为进一步的指导，“c[乙内酰脲(C(O)-(Asp-Ab))-A1-A2-A3-A4-Lys]-”表示下述化合物:而“c[乙内酰脲(C(O)-(Dap-Ab))-A1-A2-A3-A4-Asp]-”具有下述通式:
“酰基”指R”-C(O)-,其中R”是H、烷基、被取代的烷基、杂烷基、被取代的杂烷基、烯基、被取代的烯基、芳基、烷基芳基或被取代的烷基芳基,并且在具体实施方案的通式中表示为“Ac”。
“烷基”指含有一个或多个碳原子的烃基，其中多个碳原子（如果存在）通过单键连接。烷基烃基可以是直链或者含有一个或多个支链或者环状基团。
“羟基烷基”指烷基，其中烃基的一个或多个氢原子被一个或多个羟基取代，如羟基甲基、羟基乙基、羟基丙基、羟基丁基、羟基戊基、羟基己基等等。
“被取代的烷基”指烷基，其中烃基的一个或多个氢原子被选自卤素（即，氟、氯、溴和碘）、-OH、-CN、-SH、-NH2、-NHCH3、-NO2和-C1-20烷基的一个或多个取代基取代，其中所述-C1-20烷基任选可以被在每种情况下独立地选自卤素、-CF3、-OCH3、-OCF3和-(CH2)0-20-COOH的一个或多个取代基取代。在不同的实施方案中，存在1、2、3或4个取代基。-(CH2)0-20-COOH的存在导致产生烷基酸。含有或者组成为-(CH2)0-20-COOH的烷基酸的非限制性实例包括2－降冰片烷乙酸、叔丁酸、3－环戊基丙酸，等等。
术语“卤”包括氟、氯、溴和碘。
“杂烷基”指烷基，其中烃基中的一个或多个碳原子被选自下面基团的一个或多个取代：氨基、酰氨基、-O-、-S-或羰基。在不同实施方案中，存在1或2个杂原子。
“被取代的杂烷基”指杂烷基，其中烃基的一个或多个氢原子被选自卤素（即，氟、氯、溴和碘）、-OH、-CN、-SH、-NH2、-NHCH3、-NO2和-C1-20烷基的一个或多个取代基取代，其中所述-C1-20烷基任选可以被在每种情况下独立地选自卤素、-CF3、-OCH3、-OCF3和-(CH2)0-20-COOH的一个或多个取代基取代。在不同实施方案中，存在1、2、3或4个取代基。
“烯基”指由两个或多个碳组成的烃基，其中存在一个或多个碳－碳双键。烯烃基可以是直链或含有一个或多个支链或者环状基团。
“被取代的烯基”指烯基，其中一个或多个氢被选自卤素（即，氟、氯、溴和碘）、-OH、-CN、-SH、-NH2、-NHCH3、-NO2和-C1-20烷基的一个或多个取代基取代，其中所述-C1-20烷基任选可以被在每种情况下独立地选自卤素、-CF3、-OCH3、-OCF3和-(CH2)0-20-COOH的一个或多个取代基取代。在不同实施方案中，存在1、2、3或4个取代基。
“芳基”指具有至少一个环的任选被取代的芳族基团，所述环具有共轭π电子体系，其含有高达三个共轭或稠合的环体系。芳基包括碳环芳基、杂环芳基和联芳基。优选地，芳基是5-或6元环。杂环芳基的优选原子是一个或多个硫、氧和/或氮。芳基的非限制性实例包括苯基、1-萘基、2-萘基、吲哚、喹啉、2－咪唑、9－蒽，等等。芳基取代基选自-C1-20烷基、-C1-20烷氧基、卤素（即，氟、氯、溴和碘）、-OH、-CN、-SH、-NH2、-NO2、被卤素、-CF3、-OCF3、和-(CH2)0-20-COOH取代的-C1-20烷基。在不同实施方案中，芳基含有0、1、2、3或4个取代基。
“烷基芳基”指连接“芳基”的“烷基”。
术语“(C1-C12)烃部分”包括烷基、烯基和炔基，并且在烯基和炔基的情况下，为C2-C12。
为避免疑问，除非另有说明，术语被取代的意思是指被一个或更多个所定义的基团取代。当基团可从许多替代基团中选择的情况下，所选定的基团可以相同或不同。为避免疑问，术语独立地的意思是指当多于一个取代基从许多可能的取代基中选择时，这些取代基可以相同或不同。
含有碱性中心的本发明的化合物的可药用盐是例如无毒性酸加成盐，通过无机酸如盐酸、氢溴酸、氢碘酸、硫酸和磷酸，通过羧酸或通过有机磺酸形成。例子包括HCl、HBr、HI、硫酸盐或硫酸氢盐、硝酸盐、磷酸盐或磷酸氢盐、乙酸盐、苯甲酸盐、琥珀酸盐、蔗糖盐、延胡索酸盐、马来酸盐、乳酸盐、柠檬酸盐、酒石酸盐、葡萄糖酸盐、camsylate、甲磺酸盐、乙磺酸盐、苯磺酸盐、对甲苯磺酸盐和双羟萘酸盐（pamoatesalts）。本发明的化合物也提供与碱的可药用金属盐，特别是无毒性碱和碱土金属盐。例子包括钠、钾、铝、钙、镁、锌和二乙醇胺盐(Berge,S.M.等人,J.Pharm.Sci.,66:1-19(1977);Gould,P.L.,Int’lJ.Pharmaceutics,33:201-17(1986)和Bighley,L.D.等人,Encyclo.Pharma.Tech.,MarcelDekkerInc,NewYork,13:453-97(1996)。
本发明的化合物的可药用溶剂化物包括其水合物。也包含于本发明范围和本发明的多种盐中的是其多形体。此后，本发明任一方面定义的化合物其可药用盐、其溶剂化物或多形体(除了化学过程中的中间化合物)被称为“本发明的化合物”。
附图说明
图1:施用100nmole/Kg所选化合物后6小时，在禁食大鼠中消耗的食物。
图2.皮下施用75、300或600nmole/kg/天的化合物A对大鼠(A)体重、(B)累积食物摄取、(C)胰岛素水平和(D)葡萄糖水平的影响。
图3.皮下施用75、300或600nmole/kg/天的化合物B对大鼠(A)体重、(B)累积食物摄取、(C)胰岛素水平和(D)葡萄糖水平的影响。
图4.皮下施用200、600或1800nmole/kg/天的化合物A对小鼠血糖水平的影响。
图5.腹膜内施用6.4μmole/kg的化合物A对肥胖小鼠血糖水平的影响。
具体实施方式
体外研究
可以根据下面的方法测试本发明的化合物作为一种或多种黑皮质素受体配体的活性。本领域技术人员将知道类似于本文所述的方法可以用于测定本发明的化合物与黑皮质素受体分子的结合活性。
放射性配体结合测定
从稳定表达hMC-R受体亚型1、3、4或5的转基因CHO-K1细胞得到用于体外受体结合测定的细胞膜。将表达目的hMC-R受体类型的CHO-K1细胞在冰预冷的50mMTris-HCl（pH7.4）中超声处理(设置7,约30秒)然后在约4℃下以39,000g离心10分钟。将沉淀物重悬浮在相同的缓冲液中并在约4℃下以50,000g离心10分钟。经洗涤的含有细胞膜的沉淀物保存在约－80℃。
在聚丙烯96孔板中进行[125I](Tyr2)-(Nle4-D-Phe7)α-MSH([125I]-NDP-α-MSH,Amersham)结合的竞争性抑制。将如上述制备的细胞膜（1-10μg蛋白质/孔）在含有0.2%牛血清白蛋白(BSA)、5mMMgCl2、1mMCaCl2和0.1mg/mL杆菌肽与增加浓度的受试化合物和0.1-0.3nM[125I]-NDP-α-MSH的50mMTris-HCl(pH7.4)中在约37℃温育约90-120分钟。使用Packard采集器，通过预浸0.1%(w/v)聚乙烯亚胺（PEI）的GF/C玻璃纤维滤板(Packard)过滤分离结合的[125I]-NDP-α-MSH配体与游离的[125I]-NDP-α-MSH。在约0－4℃的温度下用50mMTris-HCl（pH7.4）洗涤滤器三次，然后使用Packard闪烁计数器测定放射性。通过计算机辅助的非线性回归分析(XL拟合;IDBS)分析结合数据。使用上述测定法测试一组优选实施方案并且在表5、6、7和8中报告结合常数（Ki，以nM表示）。
表5-所选化合物的放射性配体结合测定数据
表5A
表5B
表5C
表6-所选化合物的放射性配体结合测定数据
表6A
表6B
表7-通式(V)例子的结合常数
表7A
表7B–通式(VI)例子的结合常数
表7C–通式(VII)例子的结合常数
表8-所选化合物的放射性配体结合测定数据
黑皮质素功能活性和选择性
相对于其他黑皮质素受体，本发明的化合物将优先（即选择性地）与MC-4相互作用。当化合物施用于人类或其他动物时，为使与他们的施用相关的副作用的数量最小，选择性是特别重要的。本文中化合物的MC-4选择性定义为化合物对MC-1受体的EC50(EC50-MC-1)与化合物对MC-3(EC50-MC-3)/MC-4(EC50-MC-4)受体的EC50的比率,EC50值如上所述进行测量。公式如下：
MC-3选择性=[EC50-MC-1]/[EC50-MC-3]
MC-4选择性=[EC50-MC-1]/[EC50-MC-4]
当上述比率“MC-3-选择性”为至少大约10，优选地至少大约100，更优选地至少大约500时，化合物在本文中被定义为是“对MC-3受体选择性的”。
当上述比率“MC-4-选择性”为至少大约10，优选地至少大约100，更优选地至少大约500时，化合物在本文中被定义为是“对MC-4受体选择性的”。
本领域技术人员应知道如本文描述的相似的方法可用于测定本发明的化合物对黑皮质素受体分子的结合活性。
环AMP生物测定
通过电化学发光（ECL）测定法(MesoScaleGaithersburg,MD;下文中称作MSD)测定细胞内环AMP(cAMP)水平。将稳定表达hMC受体亚型的CHO-K1细胞悬浮在测定缓冲液中(RMPI1640缓冲液含有0.5mM异丁基甲基黄嘌呤(IBMX),和0.2%蛋白质混合物(MSD阻断剂A))。将稳定表达hMC受体亚型1、3、4或5的转基因CHO-K1细胞以约7,000个细胞/孔的密度分配在384-孔平板(MSD)中，该平板含有集成的碳电极并且用抗-cAMP抗体包被。加入递增浓度的受试化合物并将细胞在约37℃温育约40分钟。该温育后，加入含有0.2%蛋白质混合物和2.5nMTAGTM钌标记的cAMP(MSD)的裂解缓冲液（含有MgCl2和的HEPES缓冲的盐溶液，ph7.3)并将细胞在室温下温育约90分钟。第二次温育期结束时，加入读数缓冲液（含有ECL共反应剂和TritonX-100的Tris缓冲液，ph7.8)并用SectorImager6000(MSD)通过ECL检测立即测定细胞裂解物中的cAMP水平。使用计算机辅助的非线性回归分析(XL拟合;IDBS)分析数据并报告为EC50值或Kb值。
EC50代表得到50％的最大反应应答，例如，如使用上述测定法测定的cAMP的50％最大水平所需的激动剂化合物浓度。Kb值反映了拮抗剂的潜能并且通过Schild分析测定。简言之，在递增浓度的拮抗剂存在下进行激动剂的浓度反应曲线。Kb值是在激动剂的浓度反应曲线中将产生两倍偏移的拮抗剂浓度。通过将Schild曲线上的线外推到y轴上的0计算Kb。
使用上述测定法测试一组化合物并且结果在表9、10、11和12中报告。
表9-所选化合物的cAMP生物测定数据
表9A
ND=未测定
表9B
ND=未测定
表9C
表9D
表10A
ND=未测定
表10B
表10C
ND=未测定
表10D
表11-通式(I)例子的细胞内环AMP(cAMP)水平
表11A
表11B-
表11C
表12-所选化合物的cAMP生物测定数据
体内研究
可以根据下面的方法测试本发明的化合物对胰岛素抵抗和/或体重的影响。本领域技术人员将理解与本文所述的相似的方法可以用于测定本发明的化合物对胰岛素抵抗和/或体重的影响。
在体内研究中测试的激活黑皮质素受体的配体化合物如下（表13）：
表13
急性喂饲实验(禁食)
将雄性SpragueDawley大鼠(250g)放在单独的笼子中并在12:12小时光:暗条件下维持。在开始实验前将大鼠禁食18小时，可以自由引水。在时间0时，将大鼠用所选化合物以100nmole/kg的剂量或者用载体皮下（sc）注射，并提供食物。注射后约2、4和6小时测量个体食物消耗。在图1中报告本发明的所选化合物的数据。
慢性喂饲实验
将雄性SpragueDawley大鼠(在开始实验前已经用正常饮食（300g;ResearchDiets12450）或高脂饮食（400g;ResearchDiets12451）喂养10周)放在单独的笼子中并在12:12小时光:暗条件下维持，自由获得食物和水。麻醉大鼠并皮下植入渗透迷你泵（Alzet,Cupertino,CA）。该泵递送化合物A或化合物B（剂量为75、300或1200nmole/kg/天）或载体7天。每天测量个体体重和食物消耗。
在第7天麻醉大鼠并插颈静脉-右心房插管。在第8天进行静脉内葡萄糖耐量试验，在时间-10和0时抽取血液样品到肝素化的注射器中。在时间0时采取血液标本之后，马上通过内在插管对大鼠注射葡萄糖(1g/kg)。在2.5、5、10、20和40分钟之后抽取随后的血液样品。通过商业上可获得的试剂盒确定葡萄糖(DiagnosticChemicalsLimited)和胰岛素(Alpco)的血浆水平。结果显示于图2A-D和3A-D中。
葡萄糖耐量试验
将雄性C57BL/6小鼠(在开始实验前已经用正常饮食（30g;ResearchDiets12450）或高脂饮食（45g;ResearchDiets12452）喂养12周)放在单独的笼子中并在12:12小时光:暗条件下维持，自由获得食物和水。麻醉小鼠并皮下植入渗透迷你泵（Alzet,Cupertino,CA）。该泵递送化合物A（剂量为200、600或1800nmole/kg/天）或载体14天。在第14天对小鼠禁食18小时或过夜。在第15天通过腹膜内向小鼠注射葡萄糖(2g/kg)进行葡萄糖耐量试验。葡萄糖注射后0、15、30、60和180分钟通过尾部穿刺采集血液样品，通过Accu-Chek血糖测计仪测量血糖水平。结果显示于图4中。
将雄性Lep0b/Lep0b小鼠(50g)分组存放并在12:12小时光:暗条件下维持，自由获得食物和水。小鼠禁食18小时或过夜并进行腹膜内葡萄糖耐量试验。在-15分钟对小鼠腹膜内注射化合物A（剂量为6.4μmole/kg），通过尾部穿刺采集血液样品。在时间0时对小鼠腹膜内注射葡萄糖(1g/kg)，0、15、30、60和90分钟之后通过尾部穿刺采集血液样品，使用血糖测计仪EliteXL(BayerCorporation)测量血糖水平。结果显示于图5中。
施用和用途
本发明的肽可以以可药用盐的形式提供。此类盐的实例包括，但不限于，用有机酸（例如，乙酸、乳酸、马来酸、柠檬酸、苹果酸、抗坏血酸、琥珀酸、苯甲酸、甲磺酸、甲苯磺酸或双羟萘酸）、无机酸（例如，盐酸、硫酸或磷酸）和聚合酸（如鞣酸、羧甲基纤维素、聚乳酸、聚乙醇酸或聚乳酸－乙醇酸共聚物）形成的盐。制备本发明肽的盐的典型方法是本领域公知的并且可以通过盐交换的标准方法完成。因此，通过将本发明的肽溶解在少量0.25N乙酸水溶液中，可以将本发明肽的TFA盐（通过使用制备HPLC用含有TFA的缓冲液洗脱纯化所述肽得到的TFA盐）转化成另一种盐，如乙酸盐。将所得的溶液应用于半制备HPLC柱(300SB,C-8)。将柱子用：（1）0.1N乙酸铵水溶液洗脱0.5小时；（2）0.25N乙酸水溶液洗脱0.5小时；和（3）线性梯度（30分钟内20％到100％溶液B）以4ml/分钟的流速洗脱（溶液A是0.25N乙酸水溶液；溶液B是乙腈/水（80:20）中的0.25N乙酸）。收集含有所述肽的级分并冻干。
如本领域技术人员公知的，具有黑皮质素受体(MC-R)激动剂或拮抗剂活性的肽的已知和潜在用途是不同的和多样的，从而为了引起激动剂效果的目的，施用本发明的化合物可以具有与黑皮质素自身相同的效果和用途。
因此，本发明在其范围内包括药物组合物，其包含作为活性成分的至少一种通式（I）的化合物与可药用载体。
本发明组合物中的活性成分的剂量可以改变；然而，活性成分的量必须使得得到合适的剂型。所选的剂量依赖于所希望的治疗效果、施用途径、和治疗持续时间。通常，本发明活性的有效剂量为1x10-7到200mg/kg/天，优选1x10-4到100mg/kg/天，其可以作为单次剂量或者分成多次剂量施用。
本发明的化合物可以通过经口、肠胃外（例如，肌内、腹膜内、静脉内或皮下注射或植入）、经鼻、阴道、直肠、舌下或者局部施用途径施用并且可以与可药用载体配制以提供适于每种施用途径的剂型。
用于经口施用的固体剂型包括胶囊剂、片剂、丸剂、粉剂和粒剂。在此类固体剂型中，将活性化合物与至少一种惰性的可药用载体如蔗糖、乳糖或者淀粉混合。如此类剂型可以还包括（如常规实践）除了此类惰性稀释剂之外的额外物质，如润滑剂，如硬脂酸镁。对于胶囊剂、片剂和丸剂的情况，剂型还可以包含缓冲剂。可以额外用肠包衣制备片剂和丸剂。
用于经口施用的液体剂型包括可药用乳剂、溶液剂、混悬剂、糖浆剂、酏剂，其含有本领域常用的惰性稀释剂，如水。除了此类惰性稀释剂外，组合物可以还包括辅剂，如增湿剂、乳化和混悬剂，和增甜剂、调味剂和芳香剂。
用于肠胃外施用的根据本发明的制剂包括无菌水性或非水性溶液剂、混悬剂或乳剂。非水性溶剂或载体的实例是丙二醇、聚乙二醇、植物油，如橄榄油和玉米油、明胶和可注射的有机酯，如油酸乙酯。此类剂型还可以含有辅剂，如防腐剂、增湿剂、乳化剂和分散剂。通过例如经阻止细菌的滤器过滤、通过向组合物中掺入消毒剂，通过辐射组合物，或者通过加热组合物，可以对制剂消毒。也可以以无菌固体组合物的形式生产制剂，所述组合物可以临用前溶解在无菌水或者一些其他无菌可注射介质中。
用于直肠或阴道施用的组合物优选是栓剂，其除了活性物质外还可以含有赋形剂，如可可脂或栓剂蜡。
也可以用本领域公知的标准赋形剂制备用于经鼻或舌下施用的组合物。
此外，可以以如下面专利和专利申请中描述的那些以持续释放组合物的形式施用本发明的化合物。美国专利号5,672,659教导了包含生物活性剂和聚酯的持续释放组合物。美国专利号5,595,760教导了可胶化形式的包含生物活性剂的持续释放组合物。美国专利号5,821,221教导了包含生物活性剂和壳聚糖的聚合的持续释放组合物。美国专利号5,916,883教导了包含生物活性剂和环糊精的持续释放组合物。将前面专利和申请的教导通过引入本文作为参考。
Claims (32)
1.化合物在制备通过外周施用来治疗有其需要的受试者中胰岛素抵抗的药物中的用途，其中所述化合物选自：
Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2(SEQIDNO:50)；
乙内酰脲(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2(SEQIDNO:278)；
及其可药用盐。
2.根据权利要求1的用途，其中所述化合物是Ac-Arg-c(Cys-D-Ala-His-D-Phe-Arg-Trp-Cys)-NH2(SEQIDNO:50)或其可药用盐。
3.根据权利要求1的用途，其中所述化合物是乙内酰脲(C(O)-(Arg-Gly))-c(Cys-Glu-His-D-Phe-Arg-Trp-Cys)-NH2(SEQIDNO:278)或其可药用盐。
4.根据权利要求1-3任一项的用途，其中所述受试者是肥胖的。
5.根据权利要求1-3任一项的用途，其中所述受试者是超重的。
6.根据权利要求1-3任一项的用途，其中所述受试者是正常体重的。
7.根据权利要求1-3任一项的用途，其中所述的受试者是偏瘦的。
8.根据权利要求4的用途，其中所述肥胖的受试者罹患II型糖尿病。
9.根据权利要求5的用途，其中所述超重的受试者罹患II型糖尿病。
10.根据权利要求6的用途，其中所述正常体重的受试者罹患II型糖尿病。
11.根据权利要求7的用途，其中所述偏瘦的受试者罹患II型糖尿病。
12.根据权利要求1的用途，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。
13.根据权利要求12的用途，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。
14.根据权利要求13的用途，其中所述施用是连续的。
15.根据权利要求13的用途，其中所述施用是每天一次。
16.根据权利要求13的用途，其中所述施用是每周一次。
17.根据权利要求13的用途，其中所述施用是每两周一次。
18.根据权利要求13的用途，其中所述施用是每月一次。
19.根据权利要求13的用途，其中所述施用是每两月一次。
20.根据权利要求1的用途，其中所述外周施用也降低所述有其需要的受试者之体重。
21.根据权利要求20的用途，其中所述受试者是肥胖的。
22.根据权利要求20的用途，其中所述受试者是超重的。
23.根据权利要求21的用途，其中所述肥胖的受试者罹患II型糖尿病。
24.根据权利要求22的用途，其中所述超重的受试者罹患II型糖尿病。
25.根据权利要求20的用途，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。
26.根据权利要求25的用途，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。
27.根据权利要求26的用途，其中所述施用是连续的。
28.根据权利要求26的用途，其中所述施用是每天一次。
29.根据权利要求26的用途，其中所述施用是每周一次。
30.根据权利要求26的用途，其中所述施用是每两周一次。
31.根据权利要求26的用途，其中所述施用是每月一次。
32.根据权利要求26的用途，其中所述施用是每两月一次。
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| US11332499B2 (en) | 2018-08-16 | 2022-05-17 | Regents Of The University Of Minnesota | Cyclic peptides and methods of use thereof |
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