CN1750842A - Glp-1的类似物 - Google Patents
Glp-1的类似物 Download PDFInfo
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- CN1750842A CN1750842A CNA2004800046584A CN200480004658A CN1750842A CN 1750842 A CN1750842 A CN 1750842A CN A2004800046584 A CNA2004800046584 A CN A2004800046584A CN 200480004658 A CN200480004658 A CN 200480004658A CN 1750842 A CN1750842 A CN 1750842A
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Abstract
本发明涉及胰高血糖素样肽-1的肽类似物、其药学上可接受的盐、采用该类类似物治疗哺乳动物的方法,以及包括所述类似物的有用的药物组合物。
Description
[001]本发明所包含的“长”序列表已经以4盘CD-R的形式递交来替代打印的纸件,在此以引用的方式将该序列表的全部内容并入本文。所述的CD-R刻录于2004年2月10日,标签分别是“CRF”,″Copy 1″,″Copy 2″和″Copy3″,每一盘中只包含一个相同的456Kb的文件(129PPCT2.APP)。
发明背景
[002]本发明涉及胰高血糖素样肽-1的肽类似物、其药学上可接受的盐、用这些类似物治疗哺乳动物的方法以及包含所述类似物的有用的药物组合物。
[003]胰高血糖素样肽-1(7-36)酰胺(GLP-1)(SEQ ID NO:775)是通过胰高血糖素前体前高血糖素的组织特异性翻译后加工而在肠的L细胞中合成的(Varndell,J.M.等,J.Histochem Cytochem,1985:33:1080-6),并在进餐反应中释放到循环中。GLP-1的血浆浓度从约15pmol/L空腹水平升至40pmol/L餐后峰值。已证实,对于升高血浆葡萄糖浓度,当口服给予葡萄糖时,血浆胰岛素的增加大概比静脉内给药高出三倍(Kreymann,B.等,Lancet1987:2,1300-4)。这种胰岛素释放的饮食性增加,被称为肠降血糖作用,主要是体液性的,现在人们认为GLP-1是人类最有效的生理性肠降血糖素。除了促胰岛素作用外,GLP-1还抑制胰高血糖素分泌、延长胃排空(Wettergren A.等,Dig Dis Sci 1993:38:665-73),并可提高外周葡萄糖的利用(D′Alessio,D.A.等,J.Clin Invest 1994:93:2293-6)。
[004]1994年,根据观察提出了GLP-1的治疗效能,即观察到GLP-1的皮下(s/c)单剂量可使非胰岛素依赖型糖尿病(NIDDM)患者的餐后葡萄糖水平完全达到正常(Gutniak,M.K.等,Diabetes Care 1994:17:1039-44)。人们认为这种作用是通过增加胰岛素释放和减少胰高血糖素分泌来进行调节的。而且,已证实GLP-1的静脉内输注可延长NIDDM患者的餐后胃排空(Williams,B.等,J.Clin Endo Metab 1996:81:327-32)。与磺酰脲不同,GLP-1的促胰岛素作用依赖于血浆葡萄糖浓度(Holz,G.G.4th,等,Nature1993:361:362-5)。因此,在低血浆葡萄糖浓度时,GLP-1介导的胰岛素释放的减少可防止重度低血糖。这种结合作用使GLP-1具有超出其它目前用于治疗NIDDM的试剂的独特的潜在治疗优势。
[005]许多研究表明,当给健康人使用时,GLP-1可有效地影响升糖(glycemic)水平以及胰岛素和胰高血糖素浓度(Orskov,C,Diabetologia 35:701-711,1992;Holst,J.J.等,
Potential of GLP-1 in diahetes management inGlucagon III,Handbook of Experimental Pharmacology,Lefevbre PJ,Ed.Berlin,Springer Verlag,1996,p.311-326),这些作用是葡萄糖依赖性的(Kreymann,B.等,Lancet ii:1300-1304,1987;Weir,G.C.等,Diabetes 38:338-342,1989)。而且,它对于糖尿病患者也是有效的(Gutniak,M.,N.Engl J Med 226:1316-1322,1992;Nathan,D.M.等,Diabetes Care 15:270-276,1992),能使II型糖尿病患者的血糖水平达到正常(Nauck,M.A.等,Diagbetologia 36:741-744,1993),和改善I型糖尿病患者的升糖(glycemic)控制(Creutzfeldt,W.O.等,Diabetes Care 19:580-586,1996),增加其用作治疗剂的可能性。
[006]但是,GLP-1在代谢上是不稳定的,在体内的血浆半衰期(t1/2)仅为1-2分钟。外源性给药的GLP-1也会快速降解(Deacon,C.F.等,Diabetes44:1126-1131,1995)。这种代谢不稳定性限制了天然GLP-1的治疗效能。因此,需要一种较天然GLP-1更有效或代谢上更稳定的GLP-1类似物。
发明概述
[007]本发明的一个技术方案涉及通式(I)的化合物或其药学上可接受的盐,
[008]
(R2R3)-A7-A8-A9-A10-A11-A12-A13-A14-A15-A16-A17-A18-A19-A20-A21-A22-A23-A24-A25-A26-A27-A28-A29-A30-A31-A32-A33-A34-A35-A36-A37-A38-A39-R1,(I)
[009]其中:
[010]A7是L-His,Ura,Paa,Pta,Amp,Tma-His,去氨基-His,或不存在;
[011]A8是Abu,β-Ala,Ser,Gly或Val;
[012]A9是Glu,N-Me-Glu,N-Me-Asp或Asp;
[013]A10是Gly,Acc,β-Ala或Aib;
[014]A11是Thr或Ser;
[015]A12是Phe,Acc,Aic,Aib,3-Pal,4-Pal,1-Nal,2-Nal,Cha,Trp或X1-Phe;
[016]A13是Thr或Ser;
[017]A14是Ser或Aib;
[018]A15是Asp或Glu;
[019]A16是Val,Acc,Aib,Leu,Ile,Tle,Nle,Abu,Ala或Cha;
[020]A17是Aib,Ser或Thr;
[021]A18是Lys,Ser或Thr;
[022]A19是Tyr,Cha,Phe,3-Pal,4-Pal,Acc,1-Nal,2-Nal或X1-Phe;
[023]A20是Leu,Acc,Aib,Nle,Ile,Cha,Tle,Val,Phe或X1-Phe;
[024]A21是Glu或Asp;
[025]A22是Gly,Acc,β-Ala,Glu或Aib;
[026]A23是Gln,Asp,Asn或Glu;
[027]A24是Ala,Aib,Val,Abu,Tle或Acc;
[028]A25是Ala,Aib,Val,Abu,Tle,Acc,Lys,Arg,hArg,Orn,HN-CH((CH2)n-N(R10R11))-C(O)或HN-CH((CH2)e-X3)-C(O);
[029]A26是Lys,Arg,hArg,Om,HN-CH((CH2)n-N(R10R11))-C(O)或HN-CH((CH2)e-X3)-C(O);
[030]A27是Glu,Asp,Leu,Aib或Lys;
[031]A28是Phe,3-Pal,4-Pal,1-Nal,2-Nal,X1-Phe,Aic,Acc,Aib,Cha或Trp;
[032]A29是Ile,Acc,Aib,Leu,Nle,Cha,Tle,Val,Abu,Ala或Phe;
[033]A30是Ala,Aib或Acc;
[034]A31是Trp,-1-Nal,2-Nal,3-Pal,4-Pal,Phe,Acc,Aib或Cha;
[035]A32是Leu,Acc,Aib,Nle,Ile,Cha,Tle,Phe,X1-Phe或Ala;
[036]A33是Val,Acc,Aib,Leu,Ile,Tle,Nle,Cha,Ala,Phe,Abu,Lys或X1-Phe;
[037]A34是Lys,Arg,hArg,Orn,HN-CH((CH2)n-N(R10R11))-C(O)或HN-CH((CH2)e-X3)-C(O);
[038]A35是Gly,β-Ala,D-Ala,Gaba,Ava,HN-(CH2)m-C(O),Aib,Acc或D-氨基酸;
[039]A36是L-或D-Arg,D-或L-Lys,D-或L-hArg,D-或L-Om,HN-CH((CH2)n-N(R10R11))-C(O),HN-CH((CH2)e-X3)-C(O)或不存在;
[040]A37是Gly,β-Ala,Gaba,Ava,Aib,Acc,Ado,Arg,Asp,Aun,Aec,HN-(CH2)m-C(O),HN-CH((CH2)n-N(R10R11))-C(O),HN-CH((CH2)n-O(R10))-C(O),D-氨基酸或不存在;
[041]A38是D-或L-Lys,D-或L-Arg,D-或L-hArg,D-或L-Om,HN-CH((CH2)n-N(R10R11))-C(O),HN-CH((CH2)e-X3)-C(O)Ava,Ado,Aec或不存在;
[042]A39是D-或L-Lys,D-或L-Arg,HN-CH((CH2)n-N(R10R11))-C(O),Ava,Ado,Aec,或Aun,或不存在;
[043]每一次出现的X1独立地选自由(C1-C6)烷基,OH和卤素构成的组中;
[044]R1是OH,NH2,(C1-C30)烷氧基,或NH-X2-CH2-Z0,其中X2是(C1-C12)烃基部分,以及Z0是H,OH,CO2H或CONH2;
[046]R2和R3各自独立地选自由H,(C1-C30)烷基,(C2-C30)烯基,苯基(C1-C30)烷基,萘基(C1-C30)烷基,羟基(C1-C30)烷基,羟基(C2-C30)烯基,羟基苯基(C1-C30)烷基,以及羟基萘基(C1-C30)烷基构成的组中;或R2和R3其中之一是
(C1-C30)酰基,(C1-C30)烷基磺酰基,C(O)X5,或;
其中Y是H,OH或NH2;r是0-4;q是0-4;以及X5是(C1-C30)烷基,(C2-C30)烯基,苯基(C1-C30)烷基,萘基(C1-C30)烷基,羟基(C1-C30)烷基,羟基(C2-C30)烯基,羟基苯基(C1-C30)烷基或羟基萘基(C1-C30)烷基;
[047]每一次独立出现的e独立地为1-4的整数;
[048]每一次独立出现的m独立地为5-24的整数;
[049]每一次独立出现的n独立地为1-5的整数;
[051]每一次出现的R12和R13各自独立地为(C1-C30)烷基;
[052]条件是:
[053](i)所述的化合物不是:
[054](Ser8,β-Ala35)hGLP-1(7-36)NH2(SEQ ID NO.779);
[055](Gly8,Aib35)hGLP-1(7-36)NH2(SEQ ID NO.780);或
[056](Gly8,β-Ala35)hGLP-1(7-36)NH2(SEQ ID NO.781);
[057](ii)当A7是Ura,Paa或Pta时,则R2和R3不存在;以及
[060]通式(I)优选的一组化合物是其中A11是Thr;A13是Thr;A15是Asp;A17是Ser;A18是Ser;A21是Glu;A23是Gln或Glu;A27是Glu;以及A31是Trp的化合物或其药学上可接受的盐。
[061]上一段的化合物组中优选的一组是其中A9是Glu,N-Me-Glu或N-Me-Asp;A12是Phe,Acc或Aic;A16是Val,Acc或Aib;A19是Tyr;A20是Leu,Acc或Cha;A24是Ala,Aib或Acc;A25是Ala,Aib,Acc,Lys,Arg,hArg,Orn,HN-CH((CH2)n-N(R10R11))-C(O)或HN-CH((CH2)e-X3)-C(O);A28是Phe;A29是Ile或Acc;A30是Ala或Aib;A32是Leu,Acc或Cha;以及A33是Val或Acc的化合物或其药学上可接受的盐。
[062]上一段的化合物组中优选的一组是其中A10是Gly;A12是Phe,A6c或A5c;A16是Val,A6c或A5c;A20是Leu,A6c,A5c或Cha;A22是Gly,β-Ala或Aib;A24是Ala或Aib;A29是Ile,A6c或A5c;A32是Leu,A6c,A5c或Cha;A33是Val,A6c或A5c;A35是Aib,β-Ala,Ado,A6c,A5c或Gly;以及A37是Gly,Aib,β-Ala,Ado,D-Ala或不存在的化合物,或其药学上可接受的盐。
[063]上一段的化合物组中优选的一组是其中每次出现的X4是-C(O)-;每次出现的e为1或2;以及R1为OH或NH2的化合物或其药学上可接受的盐。
[065]第[63]段的化合物中优选的另一组化合物是其中R10是(C1-C30)酰基,(C1-C30)烷基磺酰基或
以及R11是H的化合物或其药学上可接受的盐。
[067]第[63]段的化合物中另一组优选的化合物是其中A8是Gly,Ser或Val的化合物或其药学上可接受的盐。
[068]前一段的化合物组中优选的一组是其中A8是Gly或Ser的化合物或其药学上可接受的盐。
[069]前一段的化合物组中优选的一组是下列结构式表示的化合物或其药学上可接受的盐:
[070]((Nα-Me-His)7,Gly8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.1)
[071]((Nα-Me-His)7,Gly8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.2)
[072]((Nα-Me-His)7,Gly8,Aib35,Arg26,34)hGLP-1(7-36)NH2; (SEQ ID NO.3)
[073]((Nα-Me-His)7,Gly8,Arg26,34,β-Ala35U)hGLP-1(7-36)NH2; (SEQ ID NO.4)
[074](Gly8,A6c35)hGLP-1(7-36)NH2; (SEQ ID NO.5)
[075](Gly8,A5c35)hGLP-1(7-36)NH2; (SEQ ID NO.6)
[076](Gly8,D-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.7)
[077](Gly8,Aib35,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.8)
[078](Gly8,Aib35,A5c32)hGLP-1(7-36)NH2; (SEQ ID NO.9)
[079](Gly8,Aib35,Glu23)hGLP-1(7-36)NH2; (SEQ ID NO.10)
[080](Gly8,Aib24,35)hGLP-1(7-36)NH2; (SEQ ID NO.11)
[081](Gly8,Aib30,35)hGLP-1(7-36)NH2; (SEQ ID NO.12)
[082](Gly8,Aib25,35)hGLP-1(7-36)NH2; (SEQ ID NO.13)
[083](Gly8,Aib35,A6c16,20)hGLP-1(7-36)NH2; (SEQ ID NO.14)
[084](Gly8,Aib35,A6c16,29,32)hGLP-1(7-36)NH2; (SEQ ID NO.15)
[085](Gly8,Aib35,A6c20,32)hGLP-1(7-36)NH2; (SEQ ID NO.16)
[086](Gly8,Aib35,A6c20)hGLP-1(7-36)NH2; (SEQ ID NO.17)
[087](Gly8,Aib35,Lys25)hGLP-1(7-36)NH2; (SEQ ID NO.18)
[088](Gly8,Aib24,35,A6c20)hGLP-1(7-36)NH2; (SEQ ID NO.19)
[089](Gly8,Aib35,A6c29,32)hGLP-1(7-36)NH2; (SEQ ID NO.20)
[090](Gly8,Aib24,35,A6c29,32)hGLP-1(7-36)NH2; (SEQ ID NO.21)
[091](Gly8,Aib35,A6c12)hGLP-1(7-36)NH2; (SEQ ID NO.22)
[092](Gly8,Aib35,Cha20)hGLP-1(7-36)NH2; (SEQ ID NO.23)
[093](Gly8,Aib35,A6c33)hGLP-1(7-36)NH2; (SEQ ID NO.24)
[094](Gly8,A6c16,20,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.25)
[095](Gly8,Aib35,β-Ala22)hGLP-1(7-36)NH2; (SEQ ID NO.26)
[096](Gly8,Aib22,35)hGLP-1(7-36)NH2; (SEQ ID NO.27)
[097](Gly8,Aib35,Glu23,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.28)
[098](Gly8,Aib24,35,Glu23,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.29)
[099](Gly8,Aib24,25,35,Glu23,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.30)
[0100](Gly8,Aib24,25,35,A6c16,20,32,Glu23)hGLP-1(7-36)NH2; (SEQ ID NO.31)
[0101](Gly8,A6c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.32)
[0102](Gly8,A5c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.33)
[0103](Gly8,Glu23,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.34)
[0104](Gly8,Aib24,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.35)
[0105](Gly8,Aib30,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.36)
[0106](Gly8,Aib25,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.37)
[0107](Gly8,A6c16,29,32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.38)
[0108](Gly8,A6c20,32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.39)
[0109](Gly8,A6c20,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.40)
[0110](Gly8,Lys25,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.41)
[0111](Gly8,Aib24,A6c20,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.42)
[0112](Gly8,A6c29,32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.43)
[0113](Gly8,Aib24,A6c29,32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.44)
[0114](Gly8,A6c12,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.45)
[0115](Gly8,Cha20,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.46)
[0116](Gly8,A6c33,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.47)
[0117](Gly8,β-Ala22,35)hGLP-1(7-36)NH2; (SEQ ID NO.48)
[0118](Gly8,Aib22,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.49)
[0119](Gly8,Glu23,A6c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.50)
[0120](Gly8,Aib24,Glu23,A6c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.51)
[0121](Gly8,Aib24,Glu23,A6c32,Lys34(Ne-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.52)
[0122](Gly8,Aib24,25,Glu23,A6c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.53)
[0123](Gly8,Aib24,25,A6c16,20,32,Glu23,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.54)
[0124](Gly8,Aib35,D-Arg36)hGLP-1(7-36)NH2; (SEQ ID NO.55)
[0125](Gly8,Aib35,D-Lys36)hGLP-1(7-36)NH2; (SEQ ID NO.56)
[0126](Gly8,β-Ala35,D-Arg36)hGLP-1(7-36)NH2; (SEQ ID NO.57)
[0127](Gly8,β-Ala35,D-Lys36)hGLP-1(7-36)NH2; (SEQ ID NO.58)
[0128](Gly8,Aib35,Arg26,34)hGLP-1(7-36)NH2; (SEQ ID NO.59)
[0129](Gly8,Arg26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.60)
[0130](Gly8,Aib35,Arg25,26,34)hGLP-1(7-36)NH2; (SEQ ID NO.61)
[0131](Gly8,Arg25,26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.62)
[0132](Gly8,Arg26,34,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)OH; (SEQ ID NO.63)
[0133](Gly8,Aib35,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-37)OH; (SEQ ID NO.64)
[0134](Gly8,Aib35,37,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-37)OH; (SEQ ID NO.65)
[0135](Gly8,Aib35,Arg26,34,Lys36(Nε-十四烷酰基),D-Ala37)hGLP-1(7-37)OH; (SEQ ID NO.66)
[0136](Gly8,Aib35,37,Arg26,34,Lys38(Nε-十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.67)
[0137](Gly8,Aib35,Arg26,34,β-Ala37,Lys38(Nε-十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.68)
[0138](Gly8,Aib35,Arg26,34,Lys38(Nε-十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.69)
[0139](Gly8,Arg26,34,Lys36(Nε-十四烷酰基),β-Ala37)hGLP-1(7-37)OH; (SEQ ID NO.70)
[0140](Gly8,Aib37,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-37)OH (SEQ ID NO.71)
[0141](Gly8,Aib35,Arg28,34,Ado37)hGLP-1(7-37)OH; (SEQ ID NO.72)
[0142](Gly8,Aib35,Arg26,34,Ado37)hGLP-1(7-37)NH2; (SEQ ID NO.73)
[0143](Gly8,Arg26,34,Lys36(Nε-十四烷酰基),D-Ala37)hGLP-1(7-37)OH; (SEQ ID NO.74)
[0144](Gly8,Aib37,Arg26,34,Lys38(Nε-十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.75)
[0145](Gly8,Arg26,34,β-Ala37,Lys38(Nε-十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.76)
[0146](Gly8,Aib35,Lys26(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.77)
[0147](Gly8,Aib35,Lys26(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.78)
[0148](Gly8,Aib35,Lys26(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.79)
[0149](Gly8,Lys26(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.80)
[0150](Gly8,Lys26(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.81)
[0151](Gly8,Lys26(Nε-十六烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.82)
[0152](Gly8,Aib35,Lys26(Nε-辛酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.83)
[0153](Gly8,Aib35,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.84)
[0154](Gly8,Aib35,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.85)
[0155](Gly8,Aib35,Lys26(Nε-癸酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.86)
[0156](Gly8,Aib35,Lys25,Lys26(Nε-辛酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.87)
[0157](Gly8,Aib35,Lys25,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.88)
[0158](Gly8,Aib35,Lys25,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.89)
[0159](Gly8,Aib35,Arg25,34,Lys26(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.90)
[0160](Gly8,Aib35,Arg25,34,Lys26(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.91)
[0161](Gly8,Aib35,Arg25,34,Lys26(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.92)
[0162](Gly8,Aib35,Arg25,34,Lys26(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.93)
[0163](Gly8,Lys26(Nε-辛酰基),Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.94)
[0164](Gly8,Lys26(Nε-十四烷酰基),Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.95)
[0165](Gly8,Lys26(Nε-十六烷酰基),Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.96)
[0166](Gly8,Lys26(Nε-癸酰基),Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.97)
[0167](Gly8,Aib35,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.98)
[0168](Gly8,Aib35,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.99)
[0169](Gly8,Aib35,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.100)
[0170](Gly8,Aib35,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.101)
[0171](Gly8,Aib35,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.102)
[0172](Gly8,Aib35,Arg26,Lys34(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.103)
[0173](Gly8,Aib35,Arg25,26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.104)
[0174](Gly8,Aib35,Arg25,26,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.105)
[0175](Gly8,Aib35,Arg25,26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.106)
[0176](Gly8,Aib35,Arg25,26,Lys34(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.107)
[0177](Gly8,Aib35,Lys25,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.108)
[0178](Gly8,Aib35,Lys25,Arg26,Lys34(Nε-十四烷酰基)hGLP-1(7-36)NH2; (SEQ ID NO.109)
[0179](Gly8,Aib35,Lys25,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.110)
[0180](Gly8,Aib35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.111)
[0181](Gly8,Aib35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.112)
[0182](Gly8,Aib35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.113)
[0183](Gly8,Aib35,Arg26,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.114)
[0184](Gly8,Aib35,Arg26,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.115)
[0185](Gly8,Aib35,Arg26,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.116)
[0186](Gly8,Aib35,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.117)
[0187](Gly8,Aib35,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.118)
[0188](Gly8,Aib35,Arg26,34,Lys38(Nε-辛酰基))hGLP-1(7-38)NH2; (SEQ ID NO.119)
[0189](Gly8,Aib35,Arg26,34,Lys38(Nε-癸酰基))hGLP-1(7-38)NH2; (SEQ ID NO.120)
[0190](Gly8,Aib35,Arg26,34,Lys38(Nε-十四烷酰基))hGLP-1(7-38)NH2; (SEQ ID NO.121)
[0191](Gly8,Aib35,Arg26,34,Lys38(Nε-十六烷酰基))hGLP-1(7-38)NH2; (SEQ ID NO.122)
[0192](Gly8,Aib35,37,Arg25,26,34,Lys38(Nε-辛酰基))hGLP-1(7-38)NH2; (SEQ ID NO.123)
[0193](Gly8,Aib35,37,Arg25,26,34,Lys38(Nε-癸酰基))hGLP-1(7-38)NH2; (SEQ ID NO.124)
[0194](Gly8,Aib35,37,Arg25,26,34,Lys38(Nε-十四烷酰基))hGLP-1(7-38)NH2; (SEQ ID NO.125)
[0195](Gly8,Aib35,37,Arg25,26,34,Lys38(Nε-十六烷酰基))hGLP-1(7-38)NH2; (SEQ ID NO.126)
[0196](Gly8,Aib35,37,Arg26,34,Lys38(Nε-辛酰基))hGLP-1(7-38)NH2; (SEQ ID NO.127)
[0197](Gly8,Aib35,37,Arg26,34,Lys38(Nε-癸酰基))hGLP-1(7-38)NH2; (SEQ ID NO.128)
[0198](Gly8,Aib35,37,Arg26,34,Lys38(Nε-十六烷酰基))hGLP-1(7-38)NH2; (SEQ ID NO.129)
[0199](Gly8,Aib35,Lys25,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.130)
[0200](Gly8,Aib35,Lys25,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.131)
[0201](Gly8,Aib35,Lys25,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.132)
[0202](Gly8,Aib35,Arg25,26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.133)
[0203](Gly8,Aib35,Arg25,26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.134)
[0204](Gly8,Aib35,Arg25,26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.135)
[0205](Gly8,Aib35,Arg25,26,34,Lys36(Nε-癸酰基)hGLP-1(7-36)NH2; (SEQ ID NO.136)
[0206](Gly8,Lys34(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.137)
[0207](Gly8,Lys34(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.138)
[0208](Gly8,Lys34(Nε-十六烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.139)
[0209](Gly8,A6c32,Lys34(Ne-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.140)
[0210](Gly8,Glu23,Lys34(Ne-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.141)
[0211](Gly8,Glu23,A6c32,Lys34(Ne-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.142)
[0212](Gly8,Arg26,Lys34(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.143)
[0213](Gly8,Arg26,Lys34(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.144)
[0214](Gly8,Arg26,Lys34(Nε-十六烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.145)
[0215](Gly8,Arg26,Lys34(Nε-癸酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.146)
[0216](Gly8,Arg25,26,Lys34(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.147)
[0217](Gly8,Arg25,26,Lys34(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.148)
[0218](Gly8,Arg25,26,Lys34(Nε-十六烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.149)
[0219](Gly8,Arg25,26,Lys34(Nε-癸酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.150)
[0220](Gly8,Lys25,Arg26,Lys34(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2;(SEQ ID NO.151)
[0221](Gly8,Lys25,Arg26,Lys34(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.152)
[0222](Gly8,Lys25,Arg26,Lys34(Nε-十六烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.153)
[0223](Gly8,β-Ala35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.154)
[0224](Gly8,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.155)
[0225](Gly8,β-Ala35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.156)
[0226](Gly8,Arg26,β-Ala35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.157)
[0227](Gly8,Arg26,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.158)
[0228](Gly8,Arg26,β-Ala35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.159)
[0229](Gly8,Arg26,34,β-Ala35,Lys36(Nε辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.160)
[0230](Gly8,Arg26,34,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.161)
[0231](Gly8,Arg26,34,β-Ala35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.162)
[0232](Gly8,Arg26,34,β-Ala35,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.163)
[0233](Gly8,Lys25,Arg26,34,β-Ala35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.164)
[0234](Gly8,Lys25,Arg26,34,Lys36(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.165)
[0235](Gly8,Lys25,Arg26,34,β-Ala35,Lys36(Nε- (SEQ ID NO.166)十六烷酰基))hGLP-1(7-36)NH2;
[0236](Gly8,Arg25,26,34,β-Ala35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.167)
[0237](Gly8,Arg25,26,34,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.168)
[0238](Gly8,Arg25,26,34,β-Ala35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.169)
[0239](Gly8,Arg25,26,34,β-Ala35,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.170)
[0240](Gly8,Aib35,Lys26(Nε-辛酰基),A6c32,Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.171)
[0241](Gly8,Aib35,Lys26(Nε-十四烷酰基),A6c32,Arg34)hGLP-1(7-36)NH2; (SEQ ID NO 172)
[0242](Gly8,Aib35,Lys26(Nε-十六烷酰基),A6c32,Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.173)
[0243](Gly8,Aib35,A6c32,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.174)
[0244](Gly8,Aib35,A6c32,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.175)
[0245](Gly8,Aib35,A6c32,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.176)
[0246](Gly8,Aib35,Arg26,A6c32,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.177)
[0247](Gly8,Aib35,Arg26,A6c32,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.178)
[0248](Gly8,Aib35,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.179)
[0249](Gly8,Aib35,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.180)
[0250](Gly8,Aib35,A6c32,Lys36(Nε十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.181)
[0251](Gly8,Aib35,Arg26,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.182)
[0252](Gly8,Aib35,Arg26,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.183)
[0253](Gly8,Aib35,Arg26,A6c32,Lys36(Nε十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.184)
[0254](Gly8,Aib35,Arg26,34,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.185)
[0255](Gly8,Aib35,Arg26,34,A6c32,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.186)
[0256](Gly8,Aib35,Arg26,34,A6c32,Lys36(Nε (SEQ ID NO.187)十四烷酰基))hGLP-1(7-36)NH2;
[0257](Gly8,Aib35,Arg26,34,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.188)
[0258](Gly8,Aib24,35,Lys26(Nε-辛酰基,Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.189)
[0259](Gly8,Aib24,35,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.190)
[0260](Gly8,Aib24,35,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.191)
[0261](Gly8,Aib24,35,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.192)
[0262](Gly8,Aib24,35,Arg26,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.193)
[0263](Gly8,Aib24,35,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.194)
[0264](Gly8,Aib24,35,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO 195)
[0265](Gly8,Aib24,35,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.196)
[0266](Gly8,Aib24,35,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.197)
[0267](Gly8,Aib24,35,Glu23,A6c32,Lys34(Ne-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.198)
[0268](Gly8,Aib35,Glu23,Lys26(Nε-辛酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.199)
[0269](Gly8,Aib35,Glu23,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.200)
[0270](Gly8,Aib35,Glu23,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.201)
[0271](Gly8,Aib35,Glu23,Lys34(Ne-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.202)
[0272](Gly8,Aib35,Glu23,A6c32,Lys34(Ne-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.203)
[0273](Gly8,Aib35,Glu23,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.204)
[0274](Gly8,Aib35,Glu23,Arg26,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.205)
[0275](Gly8,Aib35,Glu23,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.206)
[0276](Gly8,Aib35,Glu23,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.207)
[0277](Gly8,Aib35,Glu23,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.208)
[0278](Gly8,Aib35,Glu23,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.209)
[0279](Gly8,Aib35,Glu23,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2;(SEQ ID NO.210)
[0280](Gly8,Aib35,Glu23,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.211)
[0281](Gly8,Aib35,Glu23,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.212)
[0282](Gly8,Aib30,35,Lys26(Nε-辛酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.213)
[0283](Gly8,Aib30,35,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.214)
[0284](Gly8,Aib30,35,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.215)
[0285](Gly8,Aib30,35,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.216)
[0286](Gly8,Aib30,35,Arg26,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.217)
[0287](Gly8,Aib30,35,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.218)
[0288](Gly8,Aib30,35,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.219)
[0289](Gly8,Aib30,35,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.220)
[0290](Giy8,Aib30,35,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.221)
[0291](Gly8,Aib35,Glu23,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.222)
[0292](Gly8,Aib35,Glu23,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.223)
[0293](Gly8,Aib35,Glu23,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.224)
[0294](Gly8,Aib35,Glu23,Arg26,34,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.225)
[0295](Gly8,Aib35,Glu23,Arg26,34,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.226)
[0296](Gly8,Aib35,Glu23,Arg26,34,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.227)
[0297](Gly8,Aib24,35,Glu23,Arg26,34,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.228)
[0298](Gly8,Aib24,35,Glu23,Arg26,34,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.229)
[0299](Gly8,Aib24,35,Glu23,Arg26,34,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.230)
[0300](Gly8,Aib24,30,35,Glu23,Arg26,34,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.231)
[0301](Gly8,Aib24,30,35,Glu23,Arg26,34,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.232)
[0302](Gly8,Aib24,30,35,Glu23,Arg26,34,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.233)
[0303]((Nα-HEPES-His)7,Gly8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.234)
[0304]((Nα-HEPA-His)7,Gly8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.235)
[0305]((Nα-十四烷酰基-His)7,Gly8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.236)
[0306]((Nα-十四烷酰基-His)7,Gly8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.237)
[0307]((Nα-十四烷酰基-His)7,Gly8,Aib35,Arg26,34)hGLP-1(7-36)NH2; (SEQ ID NO.238)
[0308]((Nα-十四烷酰基-His)7,Gly8,Arg26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.239)
[0309]((Nα-十四烷酰基-His)7,Gly8,Aib35,Arg25,26,34)hGLP-1(7-36)NH2; (SEQ ID NO.240)
[0310]((Nα-十四烷酰基-His)7,Gly8,Arg25,26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.241)
[0311](Gly8,Aib35,Lys26(Nε-辛烷磺酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.242)
[0312](Gly8,Aib35,Lys26(Nε-十二烷磺酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.243)
[0313](Gly8,Aib35,Lys26(Nε十六烷磺酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.244)
[0314](Gly8,Aib35,Arg26,Lys34(Nε-辛烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.245)
[0315](Gly8,Aib35,Arg26,Lys34(Nε-十二烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.246)
[0316](Gly8,Aib35,Arg26,Lys34(Nε-十六烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.247)
[0317](Gly8,Aib35,Arg26,34,Lys36(Nε-辛烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.248)
[0318](Gly8,Aib35,Arg26,34,Lys36(Nε十六烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.249)
[0319](Gly8,Aib35,Asp26(1-(4-癸基哌嗪)),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.250)
[0320](Gly8,Aib35,Asp26(1-(4-十二烷基哌嗪)),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.251)
[0321](Gly8,Aib35,Asp26(1-(4-十四烷基哌嗪)),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.252)
[0322](Gly8,Aib35,Asp26(1-(4-十六烷基哌嗪)),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.253)
[0323](Gly8,Aib35,Arg26,Asp34(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.254)
[0324](Gly8,Aib35,Arg26,Asp34(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.255)
[0325](Gly8,Aib35,Arg26,Asp34(1-(4-十四烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.256)
[0326](Gly8,Aib35,Arg26,Asp34(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.257)
[0327](Gly8,Aib35,Arg26,34,Asp36(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.258)
[0328](Gly8,Aib35,Arg26,34,Asp36(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.259)
[0329](Gly8,Aib35,Arg26,34,Asp36(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.260)
[0330](Gly8,Aib35,Arg26,34,Asp38(1-(4-癸基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.261)
[0331](Gly8,Aib35,Arg26,34,Asp38(1-(4-十二烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.262)
[0332](Gly8,Aib35,Arg26,34,Asp38(1-(4-十四烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.263)
[0333](Gly8,Aib35,Arg26,34,Asp38(1-(4-十六烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.264)
[0334](Gly8,Aib35,37,Arg26,34,Asp38(1-(4-癸基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.265)
[0335](Gly8,Aib35,37,Arg26,34,Asp38(1-(4-十二烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.266)
[0336](Gly8,Aib35,37,Arg26,34,Asp38(1-(4-十四烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.267)
[0337](Gly8,Aib35,37,Arg26,34,Asp38(1-(4-十六烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.268)
[0338](Gly8,Aib35,Arg25,34,Asp26(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.269)
[0339](Gly8,Aib35,Arg25,34,Asp26(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.270)
[0340](Gly8,Aib35,Arg25,34,Asp26(1-(4-十四烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.271)
[0341](Gly8,Aib35,Arg25,34,Asp26(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.272)
[0342](Gly8,Aib35,Arg25,26,Asp34(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.273)
[0343](Gly8,Aib35,Arg25,26,Asp34(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.274)
[0344](Gly8,Aib35,Arg25,26,Asp34(1-(4-十四烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.275)
[0345](Gly8,Aib35,Arg25,26,Asp34(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.276)
(0346](Gly8,Aib35,Arg25,26,34,Asp36(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.277)
[0347](Gly8,Aib35,Arg25,26,34,Asp36(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.278)
[0348](Gly8,Aib35,Arg25,26,34,Asp36(1-(4-十四烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.279)
[0349](Gly8,Aib35,Arg25,26,34,Asp36(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.280)
[0350](Gly8,Aib35,Arg25,26,34,Asp38(1-(4-癸基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.281)
[0351](Gly8,Aib35,Arg25,26,34,Asp38(1-(4- (SEQ ID NO.282)十二烷基哌嗪)))hGLP-1(7-38)NH2;
[0352](Gly8,Aib35,Arg25,26,34,Asp38(1-(4-十四烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.283)
[0353](Gly8,Aib35,Arg25,26,34,Asp38(1-(4-十六烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.284)
[0354](Gly8,Aib35,37,Arg25,26,34,Asp38(1-(4-癸基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.285)
[0355](Gly8,Aib35,37,Arg25,26,34,Asp38(1-(4-十二烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.286)
[0356](Gly8,Aib35,37,Arg25,26,34,Asp38(1-(4-十四烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.287)
[0357](Gly8,Aib35,37,Arg25,26,34,Asp38(1-(4-十六烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.288)
[0358](Gly8,Aib35,Arg26,34,Glu36(1-十二烷基氨基))hGLP-1(7-36)NH2; (SEQ ID NO.289)
[0359](Gly8,Aib35,Glu26(1-十二烷基氨基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.290)
[0360](Gly8,Aib35,Arg26,Glu34(1-十二烷基氨基))hGLP-1(7-36)NH2; (SEQ ID NO.291)
[0361](Gly8,Aib35,37,Arg26,34,Glu38(1-十二烷基氨基))hGLP-1(7-38)NH2; (SEQ ID NO.292)
[0362](Gly8,Aib35,Arg34,Lys26(Nε-(2-(4-癸基-1-哌嗪)-乙酰基))hGLP-1(7-36)NH2; (SEQ ID NO.293)
[0363](Gly8,Aib35,Arg34,Lys26(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.294)
[0364](Gly8,Aib35,Arg34,Lys26(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.295)
[0365](Gly8,Aib35,Arg34,Lys26(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.296)
[0366](Gly8,Aib35,Arg26,Lys34(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.297)
[0367](Gly8,Aib35,Arg26,Lys34(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基))hGLP-1(7-36)NH2; (SEQ ID NO.298)
[0368](Gly8,Aib35,Arg26,Lys34(Nε-(2-(4-十四烷基-1-哌嗪)- (SEQ ID NO.299)乙酰基)))hGLP-1(7-36)NH2;
[0369](Gly8,Aib35,Arg26,Lys34(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.300)
[0370](Gly8,Aib35,Arg26,34,Lys36(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.301)
[0371](Gly8,Aib35,Arg26,34,Lys36(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.302)
[0372](Gly8,Aib35,Arg26,34,Lys36(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.303)
[0373](Gly8,Aib35,Arg26,34,Lys38(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.304)
[0374](Gly8,Aib35,Arg26,34,Lys38(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.305)
[0375](Gly8,Aib35,Arg26,34,Lys38(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.306)
[0376](Gly8,Aib35,Arg26,34,Lys38(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.307)
[0377](Gly8,Aib35,37,Arg26,34,Lys38(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.308)
[0378](Gly8,Aib35,37,Arg26,34,Lys38(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.309)
[0379](Gly8,Aib35,37,Arg26,34,Lys38(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.310)
[0380](Gly8,Aib35,37,Arg26,34,Lys38(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.311)
[0381](Gly8,Aib35,Arg25,34,Lys26(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.312)
[0382](Gly8,Aib35,Arg25,34,Lys26(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.313)
[0383](Gly8,Aib35,Arg25,34,Lys26(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.314)
[0384](Gly8,Aib35,Arg25,34,Lys26(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.315)
[0385](Gly8,Aib35,Arg25,26,Lys34(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.316)
[0386](Gly8,Aib35,Arg25,26,Lys34(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.317)
[0387](Gly8,Aib35,Arg25,26,Lys34(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.318)
[0388](Gly8,Aib35,Arg25,26,Lys34(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.319)
[0389](Gly8,Aib35,Arg25,26,34,Lys36(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.320)
[0390](Gly8,Aib35,Arg25,26,34,Lys36(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.321)
[0391](Gly8,Aib35,Arg25,26,34,Lys36(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.322)
[0392](Gly8,Aib35,Arg25,26,34,Lys36(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.323)
[0393](Gly8,Aib35,Arg25,26,34,Lys38(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.324)
[0394](Gly8,Aib35,Arg25,26,34,Lys38(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.325)
[0395](Gly8,Aib35,Arg25,26,34,Lys38(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.326)
[0396](Gly8,Aib35,Arg25,26,34,Lys38(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.327)
[0397](Gly8,Aib35,37,Arg25,26,34,Lys38(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.328)
[0398](Gly8,Aib35,37,Arg25,26,34,Lys38(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.329)
[0399](Gly8,Aib35,37,Arg25,26,34,Lys38(Nε-(2-(4-十四烷基-1-哌嗪)- (SEQ ID NO.330)乙酰基)))hGLP-1(7-38)NH2;
[0400](Gly8,Aib35,37,Arg25,26,34,Lys38(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.331)
[0401](Gly8,Aib35,Arg26,34,Lys36(Nε-癸酰基))hGLP-1(7-36)OH; (SEQ ID NO.332)
[0402](Gly8,Aib35,Lys25,Arg26,34,Lys36(Nε-癸酰基))hGLP-1(7-36)OH; (SEQ ID NO.333)
[0403](Gly8,Aib35,Arg26,34,Ava37,Ado38)hGLP-1(7-38)NH2; (SEQ ID NO.334)
[0404](Gly8,Aib35,Arg26,34,Asp37,Ava38,Ado39)hGLP-1(7-39)NH2; (SEQ ID NO.335)
[0405](Gly8,Aib35,Arg26,34,Aun37)hGLP-1(7-37)NH2; (SEQ ID NO.336)
[0406](Gly8,Aib17,35)hGLP-1(7-36)NH2; (SEQ ID NO.337)
[0407](Gly8,Arg26,34,β-Ala35,D-Asp37,Ava38,Aun39)hGLP-1(7-39)NH2; (SEQ ID NO.338)
[0408](Gly8,Glu22,23,β-Ala35)hGLP-1(7-36)NH2, (SEQ ID NO.339)
[0409](Gly8,Lys18,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.340)
[0410](Gly8,Leu27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.341)
[0411](Gly8,Lys33,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.342)
[0412](Gly8,Lys18,Leu27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.343)
[0413](Gly8,D-Arg36)hGLP-1(7-36)NH2; (SEQ ID NO.344)
[0414](Gly8,β-Ala35,D-Arg37)hGLP-1(7-37)NH2; (SEQ ID NO.345)
[0415](Gly8,Aib27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.346)
[0416](Gly8,Aib27,β-Ala35,37,Arg38)hGLP-1(7-38)NH2; (SEQ ID NO.347)
[0417](Gly8,Aib27,β-Ala35,37,Arg38,39)hGLP-1(7-39)NH2; (SEQ ID NO.348)
[0418](Gly8,Lys18,27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.349)
[0419](Gly8,Lys27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.350)
[0420](Gly8,β-Ala35,Arg38)hGLP-1(7-38)NH2; (SEQ ID NO.351)
[0421](Gly8,Arg26,34,β-Ala35,)hGLP-1(7-36)NH2; (SEQ ID NO.352)
[0422](Gly8,D-Arg35)hGLP-1(7-36)NH2; (SEQ ID NO.353)
[0423](Gly8,β-Ala35,Arg37)hGLP-1(7-37)NH2; (SEQ ID NO.354)
[0424](Gly8,Phe31,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.355)
[0425](Gly8,Aib35,Phe31)hGLP-1(7-36)NH2; (SEQ ID NO.356)
[0426](Gly8,Aib35,2-Nal31)hGLP-1(7-36)NH2; (SEQ ID NO.357)
[0427](Gly8,Aib35,2-Nal28,31)hGLP-1(7-36)NH2; (SEQ ID NO.358)
[0428](Gly8,Aib35,Arg26,34,2-Nal31)hGLP-1(7-36)NH2; (SEQ ID NO.359)
[0429](Gly8,Aib35,Arg26,34,Phe31)hGLP-1(7-36)NH2; (SEQ ID NO.360)
[0430](Gly8,Aib35,2-Nal19,31)hGLP-1(7-36)NH2; (SEQ ID NO.361)
[0431](Gly8,Aib35,2-Nal12,31)hGLP-1(7-36)NH2; (SEQ ID NO.362)
[0432](Gly8,Aib35,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.363)
[0433](Gly8,Aib35,Arg34,Lys26(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.364)
[0434](Gly8,Aib35,Arg26,34,Lys36(Nε-十二烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.365)
[0435](Gly8,β-Ala35,Ser37(O-癸酰基))hGLP1(7-37)-NH2; (SEQ ID NO.366)
[0436](Gly8,Aib27,β-Ala35,37,Arg38,Lys39(Nε-辛酰基))hGLP-1(7-39)NH2; (SEQ ID NO.367)
[0437](Gly8,Arg26,34,β-Ala35,Lys37(Nε-辛酰基))hGLP-1(7-37)NH2; (SEQ ID NO.368)
[0438](Gly8,Arg26,34,β-Ala35,Lys37(Nε-癸酰基))hGLP-1(7-37)NH2; (SEQ ID NO.369)
[0439](Gly8,Arg26,34,β-Ala35,Lys37(Nε-十四烷酰基))hGLP-1(7-37)NH2; (SEQ ID NO.370)
[0440](Gly8,Arg26,34,β-Ala35,Lys37(Nε-十二烷酰基))hGLP-1(7-37)NH2; (SEQ ID NO.371)
[0441](Gly8,Arg26,34,β-Ala35,Lys37(Nε-十二烷酰基))hGLP-1(8-37)NH2; (SEQ ID NO.372)
[0442](Gly8,Arg26,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.373)
[0443](Gly8,Arg26,Phe31,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.374)
[0444](Gly8,Arg26,Phe31,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.375)
[0445](Gly8,Arg26,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.376)
[0446](Gly8,Arg26,34,Phe31,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.377)
[0447](Gly8,Arg26,34,Phe31,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.378)
[0448](Gly8,Arg34,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.379)
[0449](Gly8,Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.380)
[0450](Gly8,Phe31,Arg34,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.381)
[0451](Gly8,Phe31,Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.382)
[0452](Gly8,Arg26,34,β-Ala35,Lys36(Nε-Aec-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.383)
[0453]or(Gly8,β-Ala35,Ser37(O-癸酰基))hGLP1(7-37)-NH2; (SEQ lD NO.384)
[0455]第[068]段所述的化合物组中另一优选的化合物是具有下列结构式的化合物或其药学上可接受的盐:
[0456]((Nα-Me-His)7,Ser8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.385)
[0457]((Nα-Me-His)7,Ser8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.386)
[0458]((Nα-Me-His)7,Ser8,Aib35,Arg26,34)hGLP-1(7-36)NH2; (SEQ ID NO.387)
[0459]((Nα-Me-His)7,Ser8,Arg26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.388)
[0460](Ser8,A6c35)hGLP-1(7-36)NH2; (SEQ ID NO.389)
[0461](Ser8,A5c35)hGLP-1(7-36)NH2; (SEQ ID NO.390)
[0462](Ser8,D-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.391)
[0463](Ser5,Aib35,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.392)
[0464](Ser8,Aib35,A5c32)hGLP-1(7-36)NH2; (SEQ ID NO.393)
[0465](Ser8,Aib35,Glu23)hGLP-1(7-36)NH2; (SEQ ID NO.394)
[0466](Ser8,Aib24,35)hGLP-1(7-36)NH2; (SEQ ID NO.395)
[0467](Ser8,Aib30,35)hGLP-1(7-36)NH2; (SEQ ID NO.396)
[0468](Ser8,Aib25,35)hGLP-1(7-36)NH2; (SEQ ID NO.397)
[0469](Ser8,Aib35,A6c16,20)hGLP-1(7-36)NH2; (SEQ ID NO.398)
[0470](Ser8,Aib35,A6c16,29,32)hGLP-1(7-36)NH2; (SEQ ID NO.399)
[0471](Ser8,Aib35,A6c20,32)hGLP-1(7-36)NH2; (SEQ ID NO.400)
[0472](Ser8,Aib35,A6c20)hGLP-1(7-36)NH2; (SEQ ID NO.401)
[0473](Ser8,Aib35,Lys25)hGLP-1(7-36)NH2; (SEQ ID NO.402)
[0474](Ser8,Aib24,35,A6c20)hGLP-1(7-36)NH2; (SEQ ID NO.403)
[0475](Ser8,Aib35,A6c29,32)hGLP-1(7-36)NH2; (SEQ ID NO.404)
[0476](Ser8,Aib24,35,A6c29,32)hGLP-1(7-36)NH2; (SEQ ID NO.405)
[0477](Ser8,Aib35,A6c12)hGLP-1(7-36)NH2; (SEQ ID NO.406)
[0478](Ser8,Aib35,Cha20)hGLP-1(7-36)NH2; (SEQ ID NO.407)
[0479](Ser8,Aib35,A6c33)hGLP-1(7-36)NH2; (SEQ ID NO.408)
[0480](Ser8,A6c16,20,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.409)
[0481](Ser8,Aib35,β-Ala22)hGLP-1(7-36)NH2; (SEQ ID NO.410)
[0482](Ser8,Aib22,35)hGLP-1(7-36)NH2; (SEQ ID NO.411)
[0483](Ser8,Aib35,Glu23,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.412)
[0484](Ser8,Aib24,35,Glu23,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.413)
[0485](Ser8,Aib24,25,35,Glu23,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.414)
[0486](Ser8,Aib24,25,35,A6c16,20,32,Glu23)hGLP-1(7-36)NH2; (SEQ ID NO.415)
[0487](Ser8,A6c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.416)
[0488](Ser8,A5c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.417)
[0489](Ser8,Glu23,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.418)
[0490](Ser8,Aib24,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.419)
[0491](Ser8,Aib30,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.420)
[0492](Ser8,Aib25,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.421)
[0493](Ser8,A6c16,29,32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.422)
[0494](Ser8,A6c20,32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.423)
[0495](Ser8,A6c20,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.424)
[0496](Ser8,Lys25,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.425)
[0497](Ser8,Aib24,A6c20,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.426)
[0498](Ser8,A6c29,32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.427)
[0499](Ser8,Aib24,A6c29,32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.428)
[0500](Ser8,A6c12,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.429)
[0501](Ser8,Cha20,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.430)
[0502](Ser8,A6c33,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.431)
[0503](Ser8,β-Ala22,35)hGLP-1(7-36)NH2; (SEQ ID NO.432)
[0504](Ser8,Aib22,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.433)
[0505](Ser8,Glu23,A6c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.434)
[0506](Ser8,Aib24,Glu23,A6c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.435)
[0507](Ser8,Aib24,Glu23,A6c32,Lys34(N8-octanoyl),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.436)
[0508](Ser8,Aib24,25,Glu23,A6c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.437)
[0509](Ser8,Aib24,25,A6c18,20,32,Glu23,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.438)
[0510](Ser8,Aib35,D-Arg36)hGLP-1(7-36)NH2; (SEQ ID NO.439)
[0511](Ser8,Aib35,D-Lys36)hGLP-1(7-36)NH2; (SEQ ID NO.440)
[0512](Ser8,β-Ala35,D-Arg36)hGLP-1(7-36)NH2; (SEQ ID NO.441)
[0513](Ser8,β-Ala35,D-Lys36)hGLP-1(7-36)NH2; (SEQ ID NO.442)
[0514](Ser8,Aib35,Arg26,34)hGLP-1(7-36)NH2; (SEQ ID NO.443)
[0515](Ser8,Arg26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.444)
[0516](Ser8,Aib35,Arg25,26,34)hGLP-1(7-36)NH2; (SEQ ID NO.445)
[0517](Ser8,Arg25,26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.446)
[0518](Ser8,Arg26,34,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)OH; (SEQ ID NO.447)
[0519](Ser8,Aib35,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-37)OH; (SEQ ID NO.448)
[0520](Ser8,Aib35,37,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-37)OH; (SEQ ID NO.449)
[0521](Ser8,Aib35,Arg26,34,Lys36(Nε-十四烷酰基),D-Ala37)hGLP-1(7-37)OH; (SEQ ID NO.450)
[0522](Ser8,Aib35,37,Arg26,34,Lys38(Nε-十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.451)
[0523](Ser8,Aib35,Arg26,34,β-Ala37,Lys38(Nε-十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.452)
[0524](Ser8,Aib35,Arg26,34,Lys38(Nε-十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.453)
[0525](Ser8,Arg26,34,Lys36(Nε-十四烷酰基),β-Ala37)hGLP-1(7-37)OH; (SEQ ID NO.454)
[0526](Ser8,Aib37,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-37)OH; (SEQ ID NO.455)
[0527](Ser8,Aib35,Arg26,34,Ado37)hGLP-1(7-37)OH; (SEQ ID NO.456)
[0528](Ser8,Aib35,Arg26,34,Ado37)hGLP-1(7-37)NH2; (SEQ ID NO.457)
[0529](Ser8,Arg26,34,Lys36(Nε-十四烷酰基),D-Ala37)hGLP-1(7-37)OH; (SEQ ID NO.458)
[0530](Ser8,Aib37,Arg26,34,Lys38(Nε-,十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.459)
[0531](Ser8,Arg26,34,β-Ala37,Lys38(Nε-十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.460)
[0532](Ser8,Aib35,Lys26(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.461)
[0533](Ser8,Aib35,Lys26(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.462)
[0534](Ser8,Aib35,Lys26(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.463)
[0535](Ser8,Lys26(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.464)
[0536](Ser8,Lys26(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.465)
[0537](Ser8,Lys26(Nε-十六烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.466)
[0538](Ser8,Aib35,Lys26(Nε-辛酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.467)
[0539](Ser8,Aib35,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.468)
[0540](Ser8,Aib35,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.469)
[0541](Ser8,Aib35,Lys26(Nε-癸酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.470)
[0542](Ser8,Aib35,Lys25,Lys26(Nε-辛酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.471)
[0543](Ser8,Aib35,Lys25,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.472)
[0544](Ser8,Aib35,Lys25,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.473)
[0545](Ser8,Aib35,Arg25,34,Lys26(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.474)
[0546](Ser8,Aib35,Arg25,34,Lys26(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.475)
[0547](Ser8,Aib35,Arg25,34,Lys26(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.476)
[0548](Ser8,Aib35,Arg25,34,Lys26(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.477)
[0549](Ser8,Lys26(Nε-辛酰基),Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.478)
[0550](Ser8,Lys26(Nε-十四烷酰基),Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.479)
[0551](Ser8,Lys26(Nε-十六烷酰基),Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.480)
[0552](Ser8,Lys26(Nε-癸酰基),Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.481)
[0553](Ser8,Aib35,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.482)
[0554](Ser8,Aib35,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.483)
[0555](Ser8,Aib35,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.484)
[0556](Ser8,Aib35,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.485)
[0557](Ser8,Aib35,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.486)
[0558](Ser8,Aib35,Arg26,Lys34(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.487)
[0559](Ser8,Aib35,Arg25,26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.488)
[0560](Ser8,Aib35,Arg25,26,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.489)
[0561](Ser8,Aib35,Arg25,26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.490)
[0562](Ser8,Aib35,Arg25,26,Lys34(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.491)
[0563](Ser8,Aib35,Lys25,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.492)
[0564](Ser8,Aib35,Lys25,Arg26,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.493)
[0565](Ser8,Aib35,Lys25,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.494)
[0566](Ser8,Aib35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.495)
[0567](Ser8,Aib35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.496)
[0568](Ser8,Aib35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.497)
[0569](Ser8,Aib35,Arg26,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.498)
[0570](Ser8,Aib35,Arg26,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.499)
[0571](Ser8,Aib35,Arg26,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.500)
[0572](Ser8,Aib35,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.501)
[0573](Ser8,Aib35,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.502)
[0574](Ser8,Aib35,Arg26,34,Lys38(Nε-辛酰基))hGLP-1(7-38)NH2; (SEQ ID NO.503)
[0575](Ser8,Aib35,Arg26,34,Lys38(Nε-癸酰基))hGLP-1(7-38)NH2; (SEQ ID NO.504)
[0576](Ser8,Aib35,Arg26,34,Lys38(Nε-十四烷酰基))hGLP-1(7-38)NH2; (SEQ ID NO.505)
[0577](Ser8,Aib35,Arg26,34,Lys38(Nε-十六烷酰基))hGLP-1(7-38)NH2; (SEQ ID NO.506)
[0578](Ser8,Aib35,37,Arg25,26,34,Lys38(Nε-辛酰基))hGLP-1(7-38)NH2; (SEQ ID NO.507)
[0579](Ser8,Aib35,37,Arg25,26,34,Lys38(Nε-癸酰基))hGLP-1(7-38)NH2; (SEQ ID NO.508)
[0580](Ser8,Aib35,37,Arg25,26,34,Lys38(Nε-十四烷酰基))hGLP-1(7-38)NH2; (SEQ ID NO.509)
[0581](Ser8,Aib35,37,Arg25,26,34,Lys38(Nε-十六烷酰基))hGLP-1(7-38)NH2; (SEQ ID NO.510)
[0582](Ser8,Aib35,37,Arg26,34,Lys38(Nε-辛酰基))hGLP-1(7-38)NH2; (SEQ ID NO.511)
[0583](Ser8,Aib35,37,Arg26,34,Lys38(Nε-癸酰基))hGLP-1(7-38)NH2; (SEQ ID NO.512)
[0584](Ser8,Aib35,37,Arg26,34,Lys38(Nε-十六烷酰基))hGLP-1(7-38)NH2; (SEQ ID NO.513)
[0585](Ser8,Aib35,Lys25,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.514)
[0586](Ser8,Aib35,Lys25,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.515)
[0587](Ser8,Aib35,Lys25,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.516)
[0588](Ser8,Aib35,Arg25,26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.517)
[0589](Ser8,Aib35,Arg25,26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.518)
[0590](Ser8,Aib35,Arg25,26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.519)
[0591](Ser8,Aib35,Arg25,26,34,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.520)
[0592](Ser8,Lys34(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.521)
[0593](Ser8,Lys34(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.522)
[0594](Ser8,Lys34(Nε-十六烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.523)
[0595](Ser8,A6c32,Lys34(Ne-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.524)
[0596](Ser8,Glu23,Lys34(Ne-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.525)
[0597](Ser8,Glu23,A6c32,Lys34(Ne-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.526)
[0598](Ser8,Arg26,Lys34(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.527)
[0599](Ser8,Arg26,Lys34(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.528)
[0600](Ser8,Arg26,Lys34(Nε-十六烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.529)
[0601](Ser8,Arg26,Lys34(Nε-癸酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.530)
[0602](Ser8,Arg25,26,Lys34(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.531)
[0603](Ser8,Arg25,26,Lys34(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.532)
[0604](Ser8,Arg25,26,Lys34(Nε-十六烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.533)
[0605](Ser8,Arg25,26,Lys34(Nε-癸酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.534)
[0606](Ser8,Lys25,Arg26,Lys34(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.535)
[0607](Ser8,Lys25,Arg26,Lys34(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.536)
[0608](Ser8,Lys25,Arg26,Lys34(Nε-十六烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.537)
[0609](Ser8,β-Ala35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.538)
[0610](Ser8,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.539)
[0611](Ser8,β-Ala35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.540)
[0612](Ser8,Arg26,β-Ala35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.541)
[0613](Ser8,Arg26,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.542)
[0614](Ser8,Arg26,β-Ala35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.543)
[0615](Ser8,Arg26,34,β-Ala35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.544)
[0616](Ser8,Arg26,34,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.545)
[0617](Ser8,Arg26,34,β-Ala35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.546)
[0618](Ser8,Arg26,34,β-Ala35,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.547)
[0619](Ser8,Lys25,Arg26,34,β-Ala35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.548)
[0620](Ser8,Lys25,Arg26,34,Lys36(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.549)
[0621](Ser8,Lys25,Arg26,34,β-Ala35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.550)
[0622](Ser8,Arg25,26,34,β-Ala35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.551)
[0623](Ser8,Arg25,26,34,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.552)
[0624](Ser8,Arg25,26,34,β-Ala35,Lys36(Nε- (SEQ ID NO.553)十六烷酰基))hGLP-1(7-36)NH2;
[0625](Ser8,Arg25,26,34,β-Ala35,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.554)
[0626](Ser8,Aib35,Lys26(Nε-辛酰基),A6c32,Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.555)
[0627](Ser8,Aib35,Lys26(Nε-十四烷酰基),A6c32,Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.556)
[0628](Ser8,Aib35,Lys26(Nε-十六烷酰基),A6c32,Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.557)
[0629](Ser8,Aib35,A6c32,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.558)
[0630](Ser8,Aib35,A6c32,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.559)
[0631](Ser8,Aib35,A6c32,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.560)
[0632](Ser8,Aib35,Arg26,A6c32,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.561)
[0633](Ser8,Aib35,Arg26,A6c32,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.562)
[0634](Ser8,Aib35,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.563)
[0635](Ser8,Aib35,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.564)
[0636](Ser8,Aib35,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.565)
[0637](Ser8,Aib35,Arg26,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.566)
[0638](Ser8,Aib35,Arg26,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.567)
[0639](Ser8,Aib35,Arg26,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.568)
[0640](Ser8,Aib35,Arg26,34,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.569)
[0641](Ser8,Aib35,Arg26,34,A6c32,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.570)
[0642](Ser8,Aib35,Arg26,34,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.571)
[0643](Ser8,Aib35,Arg26,34,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.572)
[0644](Ser8,Aib24,35,Lys26(Nε-辛酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.573)
[0645](Ser8,Aib24,35,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.574)
[0646](Ser8,Aib24,35,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.575)
[0647](Ser8,Aib24,35,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.576)
[0648](Ser8,Aib24,35,Arg26,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.577)
[0649](Ser8,Aib24,35,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.578)
[0650](Ser8,Aib24,35,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.579)
[0651](Ser8,Aib24,35,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2 ; (SEQ ID NO.580)
[0652](Ser8,Aib24,35,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.581)
[0653](Ser8,Aib24,35,Glu23,A6c32,Lys34(Ne-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.582)
[0654](Ser8,Aib35,Glu23,Lys26(Nε-辛酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.583)
[0655](Ser8,Aib35,Glu23,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.584)
[0656](Ser8,Aib35,Glu23,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.585)
[0657](Ser8,Aib35,Glu23,Lys34(Ne-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.586)
[0658](Ser8,Aib35,Glu23,A6c32,Lys34(Ne-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.587)
[0659](Ser8,Aib35,Glu23,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.588)
[0660](Ser8,Aib35,Glu23,Arg26,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.589)
[0661](Ser8,Aib35,Glu23,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.590)
[0662](Ser8,Aib35,Glu23,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.591)
[0663](Ser8,Aib35,Glu23,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.592)
[0664](Ser8,Aib35,Glu23,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.593)
[0665](Ser8,Aib35,Glu23,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.594)
[0666](Ser8,Aib35,Glu23,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.595)
[0667](Ser8,Aib35,Glu23,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.596)
[0668](Ser8,Aib30,35,Lys26(Nε-辛酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.597)
[0669](Ser8,Aib30,35,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.598)
[0670](Ser8,Aib30,35,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.599)
[0671](Ser8,Aib30,35,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.600)
[0672](Ser8,Aib30,35,Arg26,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.601)
[0673](Ser8,Aib30,35,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.602)
[0674](Ser8,Aib30,35,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.603)
[0675](Ser8,Aib30,35,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.6Q4)
[0676](Ser8,Aib30,35,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.605)
[0677](Ser8,Aib35,Glu23,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.606)
[0678](Ser8,Aib35,Glu23,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.607)
[0679](Ser8,Aib35,Glu23,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.608)
[0680](Ser8,Aib35,Glu23,Arg26,34,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.609)
[0681](Ser8,Aib35,Glu23,Arg26,34,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.610)
[0682](Ser8,Aib35,Glu23,Arg26,34,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.611)
[0683](Ser8,Aib24,35,Glu23,Arg26,34,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.612)
[0684](Ser8,Aib24,35,Glu23,Arg26,34,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.613)
[0685](Ser8,Aib24,35,Glu23,Arg26,34,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.614)
[0686](Ser8,Aib24,30,35,Glu23,Arg26,34,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.615)
[0687](Ser8,Aib24,30,35,Glu23,Arg26,34,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.616)
[0688](Ser8,Aib24,30,35,Glu23,Arg26,34,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.617)
[0689]((Nα-HEPES-His)7,Ser8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.618)
[0690]((Nα-HEPA-His)7,Ser8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.619)
[0691]((Nα-十四烷酰基-His)7,Ser8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.620)
[0692]((Nα-十四烷酰基-His)7,Ser8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.621)
[0693]((Nα-十四烷酰基-iis)7,Ser8,Aib35,Arg26,34)hGLP-1(7-36)NH2; (SEQ ID NO.622)
[0694]((Nα-十四烷酰基-His)7,Ser8,Arg26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.623)
[0695]((Nα-十四烷酰基-His)7,Ser8,Aib35,Arg25,26,34)hGLP-1(7-36)NH2; (SEQ ID NO.624)
[0696]((Nα-十四烷酰基-His)7,Ser8,Arg25,26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.625)
[0697](Ser8,Aib35,Lys26(Nε-辛烷磺酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.626)
[0698](Ser8,Aib35,Lys26(Nε-十二烷磺酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.627)
[0699](Ser8,Aib35,Lys26(Nε-十六烷磺酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.628)
[0700](Ser8,Aib35,Arg26,Lys34(Nε-辛烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.629)
[0701](Ser8,Aib35,Arg26,Lys34(Nε-十二烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.630)
[0702](Ser8,Aib35,Arg26,Lys34(Nε-十六烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.631)
[0703](Ser8,Aib35,Arg26,34,Lys36(Nε-辛烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.632)
[0704](Ser8,Aib35,Arg26,34,Lys36(Nε-十六烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.633)
[0705](Ser8,Aib35,Asp26(1-(4-癸基哌嗪)),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.634)
[0706](Ser8,Aib35,Asp26(1-(4-十二烷基哌嗪)),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.635)
[0707](Ser8,Aib35,Asp26(1-(4-十四烷基哌嗪)), (SEQ ID NO.636)Arg34)hGLP-1(7-36)NH2;
[0708](Ser8,Aib35,Asp26(1-(4-十六烷基哌嗪)),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.637)
[0709](Ser8,Aib35,Arg26,Asp34(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.638)
[0710](Ser8,Aib35,Arg26,Asp34(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.639)
[0711](Ser8,Aib35,Arg26,Asp34(1-(4-十四烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.640)
[0712](Ser8,Aib35,Arg26,Asp34(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.641)
[0713](Ser8,Aib35,Arg26,34,Asp36(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.642)
[0714](Ser8,Aib35,Arg26,34,Asp36(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.643)
[0715](Ser8,Aib35,Arg26,34,Asp36(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.644)
[0716](Ser8,Aib35,Arg26,34,Asp38(1-(4-癸基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.645)
[0717](Ser8,Aib35,Arg26,34,Asp38(1-(4-十二烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.646)
[0718](Ser8,Aib35,Arg26,34,Asp38(1-(4-十四烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.647)
[0719](Ser8,Aib35,Arg26,34,Asp38(1-(4-十六烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.648)
[0720](Ser8,Aib35,37,Arg26,34,Asp38(1-(4-癸基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.649)
[0721](Ser8,Aib35,37,Arg26,34,Asp38(1-(4-十二烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.650)
[0722](Ser8,Aib35,37,Arg26,34,Asp38(1-(4-十四烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.651)
[0723](Ser8,Aib35,37,Arg26,34,Asp38(1-(4-十六烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.652)
[0724](Ser8,Aib35,Arg25,34,Asp26(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.653)
[0725](Ser8,Aib35,Arg25,34,Asp26(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.654)
[0726](Ser8,Aib35,Arg25,34,Asp26(1-(4-十四烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.655)
[0727](Ser8,Aib35,Arg25,34,Asp26(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.656)
[0728](Ser8,Aib35,Arg25,26,Asp34(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.657)
[0729](Ser8,Aib35,Arg25,26,Asp34(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.658)
[0730](Ser8,Aib35,Arg25,26,Asp34(1-(4-十四烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.659)
[0731](Ser8,Aib35,Arg25,26,Asp34(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.660)
[0732](Ser8,Aib35,Arg25,26,34,Asp36(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.661)
[0733](Ser8,Aib35,Arg25,26,34,Asp36(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.662)
[0734](Ser8,Aib35,Arg25,26,34,Asp36(1-(4-十四烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.663)
[0735](Ser8,Aib35,Arg25,26,34,Asp36(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.664)
[0736](Ser8,Aib35,Arg25,26,34,Asp38(1-(4-癸基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.665)
[0737](Ser8,Aib35,Arg25,26,34,Asp38(1-(4-十二烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.666)
[0738](Ser8,Aib35,Arg25,26,34,Asp38(1-(4- (SEQ ID NO.667)十四烷基哌嗪)))hGLP-1(7-38)NH2;
[0739](Ser8,Aib35,Arg25,26,34,Asp38(1-(4-十六烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.668)
[0740](Ser8,Aib35,37,Arg25,26,34,Asp38(1-(4-癸基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.669)
[0741](Ser8,Aib35,37,Arg25,26,34,Asp38(1-(4-十二烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.670)
[0742](Ser8,Aib35,37,Arg25,26,34,Asp38(1-(4-十四烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.671)
[0743](Ser8,Aib35,37,Arg25,26,34,Asp38(1-(4-十六烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.672)
[0744](Ser8,Aib35,Arg26,34,Glu36(1-十二烷基氨基))hGLP-1(7-36)NH2; (SEQ ID NO.673)
[0745](Ser8,Aib35,Glu26(1-十二烷基氨基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.674)
[0746](Ser8,Aib35,Arg26,Glu34(1-十二烷基氨基))hGLP-1(7-36)NH2; (SEQ ID NO.675)
[0747](Ser8,Aib35,37,Arg26,34,Glu38(1-十二烷基氨基))hGLP-1(7-38)NH2; (SEQ ID NO.676)
[0748](Ser8,Aib35,Arg34,Lys26(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.677)
[0749](Ser8,Aib35,Arg34,Lys26(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.678)
[0750](Ser8,Aib35,Arg34,Lys26(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.679)
[0751](Ser8,Aib35,Arg34,Lys26(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.680)
[0752](Ser8,Aib35,Arg26,Lys34(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.681)
[0753](Ser8,Aib35,Arg26,Lys34(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基))hGLP-1(7-36)NH2; (SEQ ID NO.682)
[0754](Ser8,Aib35,Arg26,Lys34(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.683)
[0755](Ser8,Aib35,Arg26,Lys34(Nε-(2-(4-十六烷基-1-哌嗪)- (SEQ ID NO.684)乙酰基)))hGLP-1(7-36)NH2;
[0756](Ser8,Aib35,Arg26,34,Lys36(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.685)
[0757](Ser8,Aib35,Arg26,34,Lys36(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.686)
[0758](Ser8,Aib35,Arg26,34,Lys36(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.687)
[0759](Ser8,Aib35,Arg26,34,Lys38(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.688)
[0760](Ser8,Aib35,Arg26,34,Lys38(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.689)
[0761](Ser8,Aib35,Arg26,34,Lys38(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.690)
[0762](Ser8,Aib35,Arg26,34,Lys38(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.691)
[0763](Ser8,Aib35,37,Arg26,34,Lys38(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.692)
[0764](Ser8,Aib35,37,Arg26,34,Lys38(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.693)
[0765](Ser8,Aib35,37,Arg26,34,Lys38(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.694)
[0766](Ser8,Aib35,37,Arg26,34,Lys38(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.695)
[0767](Ser8,Aib35,Arg25,34,Lys26(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.696)
[0768](Ser8,Aib35,Arg25,34,Lys26(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.697)
[0769](Ser8,Aib35,Arg25,34,Lys26(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.698)
[0770](Ser8,Aib35,Arg25,34,Lys26(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.699)
[0771](Ser8,Aib35,Arg25,26,Lys34(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.700)
[0772](Ser8,Aib35,Arg25,26,Lys34(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.701)
[0773](Ser8,Aib35,Arg25,26,Lys34(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.702)
[0774](Ser8,Aib35,Arg25,26,Lys34(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.703)
[0775](Ser8,Aib35,Arg25,26,34,Lys36(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ IDNO.704)
[0776](Ser8,Aib35,Arg25,26,34,Lys36(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.705)
[0777](Ser8,Aib35,Arg25,26,34,Lys36(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.706)
[0778](Ser8,Aib35,Arg25,26,34,Lys36(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.707)
[0779](Ser8,Aib35,Arg25,26,34,Lys38(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.708)
[0780](Ser8,Aib35,Arg25,26,34,Lys38(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.709)
[0781](Ser8,Aib35,Arg25,26,34,Lys38(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.710)
[0782](Ser8,Aib35,Arg25,26,34,Lys38(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.711)
[0783](Ser8,Aib35,37,Arg25,26,34,Lys38(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.712)
[0784](Ser8,Aib35,37,Arg25,26,34,Lys38(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.713)
[0785](Ser8,Aib35,37,Arg25,26,34,Lys38(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.714)
[0786](Ser8,Aib35,37,Arg25,26,34,Lys38(Nε-(2-(4-十六烷基-1-哌嗪)- (SEQ ID NO.715)乙酰基)))hGLP-1(7-38)NH2;
[0787](Ser8,Aib35,Arg26,34,Lys36(Nε-癸酰基))hGLP-1(7-36)OH; (SEQ ID NO.716)
[0788](Ser8,Aib35,Lys25,Arg26,34,Lys36(Nε-癸酰基))hGLP-1(7-36)OH; (SEQ ID NO.717)
[0789](Ser8,Aib35,Arg26,34,AVa37,Ado38)hGLP-1(7-38)NH2; (SEQ ID NO.718)
[0790](Ser8,Aib35,Arg26,34,Asp37,Ava38,Ado39)hGLP-1(7-39)NH2; (SEQ ID NO.719)
[0791](Ser8,Aib35,Arg26,34,Aun37)hGLP-1(7-37)NH2; (SEQ ID NO.720)
[0792](Ser8,Aib17,35,)hGLP-1(7-36)NH2; (SEQ ID NO.721)
[0793](Ser8,Arg26,34,β-Ala35,D-Asp37,Ava38,Aun39)hGLP-1(7-39)NH2;(SEQ ID NO.722)
[0794](Ser8,Glu22,23,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.723)
[0795](Ser8,Lys18,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.724)
[0796](Ser8,Leu27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.725)
[0797](Ser8,Lys33,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.726)
[0798](Ser8,Lys18,Leu27,β-Ala35)hGLp-1(7-36)NH2; (SEQ ID NO.727)
[0799](Ser8,D-Arg36)hGLP-1(7-36)NH2; (SEQ ID NO.728)
[0800](Ser8,β-Ala35,D-Arg37)hGLP-1(7-37)NH2; (SEQ ID NO.729)
[0801](Ser8,Aib27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.730)
[0802](Ser8,Aib27,β-Ala35,37,Arg38)hGLP-1(7-38)NH2; (SEQ ID NO.731)
[0803](Ser8,Aib27,β-Ala35,37,Arg38,39)hGLP-1(7-39)NH2; (SEQ ID NO.732)
[0804](Ser8,Lys18,27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.733)
[0805](Ser8,Lys27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.734)
[0806](Ser8,β-Ala35,Arg38)hGLP-1(7-38)NH2; (SEQ ID NO.735)
[0807](Ser8,Arg26,34,β-Ala35,)hGLP-1(7-36)NH2; (SEQ ID NO.736)
[0808](Ser8,D-Arg35)hGLP-1(7-36)NH2; (SEQ ID NO.737)
[0809](Ser8,β-Ala35,Arg37)hGLP-1(7-37)NH2; (SEQ ID NO.738)
[0810](Ser8,Phe31,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.739)
[0811](Ser8,Aib35,Phe31)hGLP-1(7-36)NH2; (SEQ ID NO.740)
[0812](Ser8,Aib35,2-Nal31)hGLP-1(7-36)NH2; (SEQ ID NO.741)
[0813](Ser8,Aib35,2-Nal28,31)hGLP-1(7-36)NH2; (SEQ ID NO.742)
[0814](Ser8,Aib35,Arg26,34,2-Nal31)hGLP-1(7-36)NH2; (SEQ ID NO.743)
[0815](Ser8,Aib35,Arg26,34,Phe31)hGLP-1(7-36)NH2; (SEQ ID NO.744)
[0816](Ser8,Aib35,2-Nal19,31)hGLP-1(7-36)NH2; (SEQ ID NO.745)
[0817](Ser8,Aib35,2-Nal12,31)hGLP-1(7-36)NH2; (SEQ ID NO.746)
[0818](Ser8,Aib35,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.747)
[0819](Ser8,Aib35,Arg34,Lys26(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.748)
[0820](Ser8,Aib35,Arg26,34,Lys36(Nε-十二烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.749)
[0821](Ser8,β-Ala35,Ser37(O-十二烷酰基))hGLP1(7-37)-NH2; (SEQ ID NO.750)
[0822](Ser8,Aib27,β-Ala35,37,Arg38,Lys39(Nε-辛酰基))hGLP-1(7-39)NH2; (SEQ ID NO.751)
[0823](Ser8,Arg26,34,β-Ala35,Lys37(Nε-辛酰基))hGLP-1(7-37)NH2; (SEQ ID NO.752)
[0824](Ser8,Arg26,34,β-Ala35,Lys37(Nε-癸酰基))hGLP-1(7-37)NH2; (SEQ ID NO.753)
[0825](Ser8,Arg26,34,β-Ala35,Lys37(Nε-十四烷酰基))hGLP-1(7-37)NH2; (SEQ ID NO.754)
[0826](Ser8,Arg26,34,β-Ala35,Lys37(Nε-十二烷酰基))hGLP-1(7-37)NH2; (SEQ ID NO.755)
[0827](Ser8,Arg26,34,β-Ala35,Lys37(Nε-十二烷酰基))hGLP-1(8-37)NH2; (SEQ ID NO.756)
[0828](Ser8,Arg26,34,β-Ala35,Lys36(Nε-Aec-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.757)
[0829](Ser8,Arg26,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.758)
[0830](Ser8,Arg26,Phe31,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.759)
[0831](Ser8,Arg26,Phe31,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.760)
[0832](Ser8,Arg26,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.761)
[0833](Ser8,Arg26,34,Phe31,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.762)
[0834](Ser8,Arg34,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.763)
[0835](Ser8,Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.764)
[0836](Ser8,Phe31,Arg34,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.765)
[0837]or(Ser8,Phe31,Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.766)
[0839]第[068]-[0453]段所述的化合物中优选的一组是下列结构式表示的化合物或其药学上可接受的盐:
[0840](Gly8,Aib35,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.8)
[0841](Gly8,Aib35,Glu23)hGLP-1(7-36)NH2; (SEQ ID NO.10)
[0842](Gly8,Aib24,35)hGLP-1(7-36)NH2; (SEQ ID NO.11)
[0843](Gly8,Aib35,Glu23,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.28)
[0844](Gly8,Glu23,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.34)
[0845](Gly8,Aib35,Arg26,34)hGLP-1(7-36)NH2; (SEQ ID NO.59)
[0846](Gly8,Aib35,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.117)
[0847](Gly8,Aib35,Arg26,34,Lys36(Nε-癸酰基))hGLP-1(7-36)OH; (SEQ ID NO.332)
[0848](Gly8,Aib35,Lys25,Arg26,34,Lys36(Nε-癸酰基))hGLP-1(7-36)OH; (SEQ ID NO.333)
[0849](Gly8,Arg26,34,β-Ala35,Lys36(Nε-Aec-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.383)
[0850](Gly8,Aib35,Arg26,34,Ava37,Ado38)hGLP-1(7-38)NH2; (SEQ ID NO.334)
[0851](Gly8,Aib35,Arg26,34,Asp37,Ava38,Ado39)hGLP-1(7-39)NH2; (SEQ ID NO.335)
[0852](Gly8,Aib35,Arg26,34,Aun37)hGLP-1(7-37)NH2; (SEQ ID NO.336)
[0853](Gly8,Aib17,35)hGLP-1(7-36)NH2; (SEQ ID NO.337)
[0854](Gly8,Arg26,34,β-Ala35,D-Asp37,Ava38,Aun39)hGLP-1(7-39)NH2;(SEQ ID NO.338)
[0855](Gly8,Glu22,23,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.339)
[0856](Gly8,Lys18,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.340)
[0857](Gly8,Leu27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.341)
[0858](Gly8,Lys33,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.342)
[0859](Gly8,Lys18,Leu27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.343)
[0860](Gly8,D-Arg36)hGLP-1(7-36)NH2; (SEQ ID NO.344)
[0861](Gly8,β-Ala35,D-Arg37)hGLP-1(7-37)NH2; (SEQ ID NO.345)
[0862](Gly8,Aib27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.346)
[0863](Gly8,Aib27,β-Ala35,37,Arg38)hGLP-1(7-38)NH2; (SEQ ID NO.347)
[0864](Gly8,Aib27,β-Ala35,37,Arg38,39)hGLP-1(7-39)NH2; (SEQ ID NO.348)
[0865](Gly8,Lys18,27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.349)
[0866](Gly8,Lys27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.350)
[0867](Gly8,β-Ala35,Arg38)hGLP-1(7-38)NH2; (SEQ ID NO.351)
[0868](Gly8,Arg26,34,β-Ala35,)hGLP-1(7-36)NH2; (SEQ ID NO.352)
[0869](Gly8,D-Arg35)hGLP-1(7-36)NH2; (SEQ ID NO.353)
[0870](Gly8,β-Ala35,Arg37)hGLP-1(7-37)NH2; (SEQ ID NO.354)
[0871](Gly8,Phe31,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.355)
[0872](Gly8,Aib35,Phe31)hGLP-1(7-36)NH2; (SEQ ID NO.356)
[0873](Gly8,Aib35,2-Nal31)hGLP-1(7-36)NH2; (SEQ ID NO.357)
[0874](Gly8,Aib35,2-Nal28,31)hGLP-1(7-36)NH2; (SEQ ID NO.358)
[0875](Gly8,Aib35,Arg26,34,2-Nal31)hGLP-1(7-36)NH2; (SEQ ID NO.359)
[0876](Gly8,Aib35,Arg26,34,Phe31)hGLP-1(7-36)NH2; (SEQ ID NO.360)
[0877](Gly8,Aib35,2-Nal19,31)hGLP-1(7-36)NH2; (SEQ ID NO.361)
[0878](Gly8,Aib35,2-Nal12,31)hGLP-1(7-36)NH2; (SEQ ID NO.362)
[0879](Gly8,Aib35,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.99)
[0880](Gly8,Aib35,Arg34,Lys26(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.364)
[0881](Gly8,Aib35,Arg26,34,Lys36(Nε-十二烷酰基)hGLP-1(7-36)NH2; (SEQ ID NO.365)
[0882](Gly8,β-Ala35,Ser37(O-癸酰基))hGLP1(7-37)-NH2; (SEQ ID NO.384)
[0883](Gly8,Aib27,β-Ala35,37,Arg38,Lys39(Nε-辛酰基))hGLP-1(7-39)NH2;(SEQ ID NO.367)
[0884](Gly8,Arg26,34,β-Ala35,Lys37(Nε-辛酰基))hGLP-1(7-37)NH2; (SEQ ID NO.368)
[0885](Gly8,Arg26,34,β-Ala35,Lys37(Nε-癸酰基))hGLP-1(7-37)NH2; (SEQ ID NO.369)
[0886]or(Gly8,Arg26,34,β-Ala35,Lys37(Nε-十四烷酰甚))hGLP-1(7-37)NH2; (SEQ ID NO.370)
[0888]第[0455]-[0837]段所述的化合物中优选的一组是下列结构式表示的化合物或其药学上可接受的盐:
[0889](Ser8,Aib35,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.392)
[0890](Ser8,Aib35,Glu23)hGLP-1(7-36)NH2; (SEQ ID NO.394)
[0891](Ser8,Aib24,35)hGLP-1(7-36)NH2; (SEQ ID NO.395)
[0892](Ser8,Aib35,Glu23,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.412)
[0893](Ser8,Glu23,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.418)
[0894](Ser8,Aib35,Arg26,34)hGLP-1(7-36)NH2; (SEQ ID NO.443)
[0895](Ser8,Aib35,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.501)
[0896](Ser8,Aib35,Arg26,34,Lys36(Nε-癸酰基))hGLP-1(7-36)OH; (SEQ ID NO.716)
[0897](Ser8,Aib35,Lys25,Arg26,34,Lys36(Nε-癸酰基))hGLP-1(7-36)OH; (SEQ ID NO.717)
[0898](Ser8,Arg26,34,β-Ala35,Lys36(Nε-Aec-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.757)
[0899](Ser8,Aib35,Arg26,34,Ava37,Ado38)hGLP-1(7-38)NH2; (SEQ ID NO.718)
[0900](Ser8,Aib35,Arg26,34,Asp37,Ava38,Ado39)hGLP-1(7-39)NH2; (SEQ ID NO.719)
[0901](Ser8,Aib35,Arg26,34,Aun37)hGLP-1(7-37)NH2; (SEQ ID NO.720)
[0902](Ser8,Aib17,35)hGLP-1(7-36)NH2; (SEQ ID NO.389)
[0903](Ser8,Arg26,34,β-Ala35,D-Asp37,Ava38,Aun39)hGLP-1(7-39)NH2;(SEQ ID NO.722)
[0904](Ser8,Glu22,23,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.723)
[0905](Ser8,Lys18,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.724)
[0906](Ser8,Leu27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.725)
[0907](Ser8,Lys33,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.726)
[0908](Ser8,Lys18,Leu27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.727)
[0909](Ser8,D-Arg36)hGLP-1(7-36)NH2; (SEQ ID NO.728)
[0910](Ser8,β-Ala35,D-Arg37)hGLP-1(7-37)NH2; (SEQ ID NO.729)
[0911](Ser8,Aib27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.730)
[0912](Ser8,Aib27,β-Ala35,37,Arg38)hGLP-1(7-38)NH2; (SEQ ID NO.731)
[0913](Ser8,Aib27,β-Ala35,37,Arg38,39)hGLP-1(7-39)NH2; (SEQ ID NO.732)
[0914](Ser8,Lys18,27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.733)
[0915](Ser8,Lys27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.734)
[0916](Ser8,β-Ala35,Arg38)hGLP-1(7-38)NH2; (SEQ ID NO.735)
[0917](Ser8,Arg26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.736)
[0918](Ser8,D-Arg35)hGLP-1(7-36)NH2; (SEQ ID NO.737)
[0919](Ser8,β-Ala35,Arg37)hGLP-1(7-37)NH2; (SEQ ID NO.738)
[0920](Ser8,Phe31,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.739)
[0921](Ser8,Aib35,Phe31)hGLP-1(7-36)NH2; (SEQ ID NO.740)
[0922](Ser8,Aib35,2-Nal31)hGLP-1(7-36)NH2; (SEQ ID NO.741)
[0923](Ser8,Aib35,2-Nal28,31)hGLP-1(7-36)NH2; (SEQ ID NO.742)
[0924](Ser8,Aib35,Arg26,34,2-Nal31)hGLP-1(7-36)NH2; (SEQ ID NO.743)
[0925](Ser8,Aib35,Arg26,34,Phe31)hGLP-1(7-36)NH2; (SEQ ID NO.744)
[0926](Ser8,Aib35,2-Nal19,31)hGLP-1(7-36)NH2; (SEQ ID NO.745)
[0927](Ser8,Aib35,2-Nal12,31)hGLP-1(7-36)NH2; (SEQ ID NO.746)
[0928](Ser8,Aib35,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.483)
[0929](Ser8,Aib35,Arg34,Lys26(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.748)
[0930](Ser8,Aib35,Arg26,34,Lys36(Nε-十二烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.749)
[0931](Ser8,β-Ala35,Ser-37(O-十二烷酰基))hGLP1(7-37)-NH2; (SEQ ID NO.539)
[0932](Ser8,Aib27,β-Ala35,37,Arg38,Lys39(Nε-辛酰基))hGLP-1(7-39)NH2; (SEQ ID NO.751)
[0933](Ser8,Arg26,34,β-Ala35,Lys37(Nε-辛酰基))hGLP-1(7-37)NH2; (SEQ ID NO.752)
[0934](Ser8,Arg26,34,β-Ala35,Lys37(Nε-癸酰基))hGLP-1(7-37)NH2; (SEQ ID NO.753)
[0935]or(Ser8,Arg26,34,β-Ala35,Lys37(Nε-十四烷酰基))hGLP-1(7-37)NH2; (SEQ ID NO.754)
[0937]在一种更优选的实施方式中,本发明以通式(I)的化合物为特征,其中所述的化合物是:
[0938](Ser8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.767)
[0939](Abu8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.768)
[0940](Val8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID N0.769)
[0941](β-Ala8,35)hGLP-1(7-36)NH2; (SEQ ID NO.770)
[0942](Abu8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.771)
[0943](Val8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.772)
[0944]或(β-Ala8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.773)
[0945]或其药学上可接受的盐。
[0946]在一种更优选的实施方式中,本发明以通式(I)的化合物为特征,其中所述的化合物是:
[0947](Ser8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.767)
[0948](Abu8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.768)
[0949]或(Abu8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.771)
[0950]或其药学上可接受的盐。
[0951]在一种进一步优选的实施方式中,本发明以通式(I)的化合物为特征,其中所述的化合物是:
[0952](Ser8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.767)
[0953]或其药学上可接受的盐。
[0954]本发明另一个技术方案是一种药物组合物,该药物组合物包括有效量的通式(I)化合物或其药学上可接受的盐,以及药学上可接受的载体或稀释剂。
[0955]本发明另一个技术方案是一种从需要的患者的GLP-1受体引起激动剂作用的方法,所述方法包括以有效量的通式(I)化合物或其药学上可接受的盐向所述的患者给药。
[0956]本发明另一技术方案是一种在患者上治疗以下疾病的方法:I型糖尿病、II型糖尿病、肥胖症、胰高血糖素瘤、气管分泌性疾病、代谢性疾病、关节炎、骨质疏松症、中枢神经系统疾病、再狭窄和神经变性疾病,所述的方法包括以有效量的通式(I)化合物或其药学上可接受的盐向所述患者给药。优选地,所述的疾病是I型糖尿病或II型糖尿病。
[0957]在第[0953],[0955]和[0956]段详述的每一技术方案的优选实施方式中,所述的通式(I)化合物为第[060],[061],[062],[063],[064],[065],[066],[067]或[068]段中所述的化合物或其药学上可接受的盐。更优选地,所述通式(I)的化合物是选自本文中具体公开的通式(I)化合物或其药学上可接受的盐。更优选地,所述的通式(I)化合物是选自第[069]-[0452]段或第[0455]-[0836]段中所公开的化合物或其药学上可接受的盐。更优选地,所述通式(I)的化合物是选自第[0839]-[0885]段或第[0888]-[0934]段中公开的化合物或其药学上可接受的盐。还优选的通式(I)化合物是选自第[0937]-[0943]段公开的化合物或其药学上可接受的盐。更优选的通式(I)化合物是选自第[0946]-[0948]段公开的化合物或其药学上可接受的盐。在一种最优选的实施方式中,所述的通式(I)化合物是(Ser8,Aib35)hGLP-1(7-36)NH2(SEQ ID NO.767)或其药学上可接受的盐。
[0958]除了N-末端氨基酸外,本公开中所有氨基酸的缩写(如Ala)代表-NH-CH(R)-CO-的结构,其中R为氨基酸的侧链(如,Ala的CH3)。对于N-末端氨基酸,缩写代表(R2R3)-N-CH(R)-CO-的结构,其中R为氨基酸的侧链,R2和R3如上所述,但当A7为Ura、Paa或Pta时,由于认为Ura,Paa和Pta是去氨基的氨基酸,这种情况下R2和R3不存在。本文中所采用的氨基酸的某些其它缩写的含义如下:
Abu α-氨基丁酸;
Ado 12-氨基十二烷酸;
Aec 4-(2-氨基乙基)-1-羧基甲基-哌嗪,由下列结构表示:
Aib α-氨基异丁基酸;
Aic 2-氨基茚满-2-羧酸;
β-Ala β-丙氨酸;
Amp 4-氨基-苯基丙氨酸;
Aun 11-氨基十一烷酸;
Ava 5-氨基戊酸;
Cha 环己基丙氨酸;
Gaba γ-氨基丁酸;
hArg 高精氨酸;
HEPA 4-(2-羟基乙基)-1-哌嗪基乙酸;
HEPES 4-(2-羟基乙基)-1-哌嗪-乙磺酸;
N-Me-Ala N-甲基-丙氨酸;
N-Me-Asp N-甲基-天冬氨酸;
N-Me-Glu N-甲基-谷氨酸;
N-Me-Gly N-甲基-甘氨酸;
Nα-Me-His Nα-甲基-组氨酸;
1-Nal β-(1-萘基)丙氨酸;
2-Nal β-(2-萘基)丙氨酸;
Nle 正亮氨酸;
Om 鸟氨酸;
Paa 反式-3-(3-吡啶基)丙烯酸;
3-Pal β-(3-吡啶基)丙氨酸;
4-Pal β-(4-吡啶基)丙氨酸;
Pta (4-吡啶基硫代)乙酸;
Tle 叔丁基甘氨酸;
Tma-His N,N-四甲基脒基-组氨酸;
Tba 叔丁基丙氨酸;以及
Ura 尿刊酸。
[0959]Acc的含义是选自下列组中的氨基酸:1-氨基-1-环丙烷羧酸(A3c);1-氨基-1-环丁烷羧酸(A4c);1-氨基-1-环戊烷羧酸(A5c);1-氨基-1-环己烷羧酸(A6c);1-氨基-1-还庚烷羧酸(A7c);1-氨基-1-环辛烷羧酸(A8c);以及1-氨基-1-环壬烷羧酸(A9c)。
[0960]术语羟基烷基,羟基苯基烷基和羟基萘基烷基每一个都是指含有1,2,3或4个羟基取代基的基团部分。
[0961]术语COX5表示-C=O.X5。-C=O.X5的例子包括但不限于乙酰基和苯基丙酰基。
[0962]Lys(Nε-烷酰基)由下列结构表示:
[0963]Lys(Nε-烷基磺酰基)由下列结构表示:
[0964]Lys(Nε-(2-(4-烷基-1-哌嗪)-乙酰基)由下列结构表示:
[0965]Asp(1-(4-烷基-哌嗪))由下列结构表示:
[0966]Asp(1-烷基氨基)由下列结构表示:
[0967]LYs(Nε-Aec-烷酰基)由下列结构表示:
[0968]Lys(Nε-ace-烷酰基)由下列结构表示:
[0969]Ser(O-烷酰基)由下列结构表示:
[0970]表示Lys(Nε-烷酰基),Lys(Nε-烷基磺酰基),Lys(Nε-(2-(4-烷基-1-哌嗪)-乙酰基)),Asp(1-(4-烷基-哌嗪)),Asp(1-烷基氨基),Lys(Nε-Aec-烷酰基),(Nε-ace-烷酰基)和Ser(O-烷酰基)的结构中的n是1-30的整数。
[0971]本文中采用的其它缩写的全称如下:
Boc t-丁基氧羰基;
2BrZ 2-溴苄基氧羰基;
Bzl 苄基;
2ClZ 2-氯苄基氧羰基;
DCM 二氯甲烷;
DIEA 二异丙基乙胺;
DMF 二甲基甲酰胺;
DNP 2,4-二硝基苯基;
Fm 甲酰基;
Fmoc 9-芴基甲氧基羰基;
HBTU 六氟磷酸2-(1H-苯并三唑-1-基)-1,1,3,3-四甲基脲鎓盐;
HF 氟化氢;
HOAc 乙酸;
HOBt N-羟基苯并三唑;
OcHex O-环己基;
PAM树脂 4-羟甲基苯基乙酰胺甲基树脂;
TFA 三氟乙酸;
Tos 甲苯磺酰基;以及
Xan 呫吨基。
[0972]术语“(C1-C30)烃基部分”包括烷基,烯基和炔基,在烯基和炔基的情况下为C2-C30烯基或炔基。
[0973]术语“卤素”包括氟,氯,溴和碘。
[0974]在本文中,本发明的肽也可以由另一种形式表示,如(A5c8)hGLP-1(7-36)NH2(SEQ ID NO.774),其中在第一对括号之间存在天然序列的取代氨基酸(如,用A5c8取代hGLP-1中的Ala8)。缩写GLP-1是指胰高血糖素样肽-1;hGLP-1是指人类胰高血糖素样肽-1。″hGLP-1″之后的括号内的数字是指该肽中存在的氨基酸的数目。例如,hGLP-1(7-36)(SEQ ID NO.775)是指人类GLP-1的肽序列中有7-36个氨基酸。hGLP-1(7-37)(SEQ ID NO.776)的序列被公开于Mojsov,S.,Int.J.Peptide Protein Res,.40,1992,pp.333-342中。hGLP-1(7-36)NH2中的″NH2″是指肽的C-末端被酰胺化。hGLP-1(7-36)(SEQ ID NO.775)是指C-末端是游离酸。对于hGLP-1(7-38)(SEQ ID NO.777),在第37和38位上的残基分别是Gly和Arg。
发明详述
[0975]本发明的肽可通过标准的固相肽合成法来制备,参见例如Stewart,J.M.等,Solid Phase Synthesis(Pierce Chemical Co.,2d ed.,1984)。上述通式的取代基R2和R3可通过本领域已知的标准方法与N-末端氨基酸的游离胺相连。例如,烷基基团,如(C1-C30)烷基,可通过还原烷基化作用连接。羟基烷基基团,如(C1-C30)羟基烷基,也可通过还原烷基化作用连接,其中游离羟基被叔丁基酯保护。酰基基团,如COE1,可通过将游离酸如E1COOH以下述方法偶联到N末端氨基酸的游离胺上而连接,所述的方法为在二氯甲烷中将完全的树脂与3摩尔当量的游离酸和二异内基碳化二亚胺混合1小时。如果游离酸包含自由羟基,例如对-羟苯基丙酸,则应该用额外的3摩尔当量HOBT进行偶联。
[0976]当R1为NH-X2-CH2-CONH2时(即Z0=CONH2),用与MBHA树脂偶联的Boc-HN-X2-CH2-COOH开始肽的合成。当R1为NH-X2-CH2-COOH时(即Z0=COOH),用与PAM树脂偶联的Boc-HN-X2-CH2-COOH开始肽的合成。对于这一特殊步骤,采用4mol当量的Boc-HN-X2-CH2-COOH,HBTU和HOBt以及10摩尔当量的DIEA。偶联时间是8小时。
[0977]受到保护的氨基酸1-(N-叔丁氧基羰基-氨基)-1-环己烷-羧酸(Boc-A6c-OH)的合成方法如下。将19.1g(0.133mol)1-氨基-1-环己烷羧酸(Acros Organics,Fisher Scientific,Pittsburgh,PA)溶解于200ml二噁烷和100ml水中。向其中加入2N NaOH 67ml,并在冰水浴中冷却该溶液。将32.0g(0.147mol)二碳酸二叔丁基酯加入到溶液中,使溶液在室温下搅拌过夜。然后在减压下除去二噁烷,并向残余的水溶液中加入200ml乙酸乙酯。在冰水浴中冷却该混合物,通过加入4N HCl将水层的pH调节至约3。分离出有机层后,用乙酸乙酯(1×100ml)萃取水层。合并两个有机层,用水(2×150ml)洗涤,然后用无水MgSO4干燥,过滤,并在减压下浓缩至干燥。残余物在乙酸乙酯/己烷中进行重结晶,得到9.2g(0.0386mol)纯化的产物,即从起始原料出发的收率为29%。
[0978]Boc-A5c-OH的合成方法与Boc-A6c-OH的合成方法类似。本领域的普通技术人员按照本文的教导采用类似的方式制备出其它受保护的Acc氨基酸。
[0979]在本发明含有A5c,A6c,Aib,Boc-Lys(2ClZ)-OH和/或Boc-His(DNP)-OH的GLP-1类似物的合成中,对这些残基和紧随其后的残基的偶联时间是2hrs。否则,偶联时间则为约5分钟。为合成(Tma-His7)hGLP-1(7-36)NH2(SEQ ID NO.778),在最终的偶联反应中,采用存在于4ml DMF中的HBTU(2mmol)和DIEA(1.0ml)与肽-树脂的N-末端自由胺进行反应;偶联时间是2小时。
[0980]可通过本领域公知的标准方法将上述通式中的取代基R2和R3连接到N-末端氨基酸的自由胺上。例如,烷基基团,如(C1-C30)烷基可采用还原性烷基化反应进行连接。羟基烷基基团,如(C1-C30)羟基烷基也可采用其中自由羟基受到叔丁基酯保护的还原性烷基化反应进行连接。酰基基团,如COX1,可通过将游离酸如X1COOH偶联到N-末端氨基酸的自由胺上而进行连接,偶联方法是将完全的树脂和3摩尔当量的游离酸和二异丙基碳化二亚胺在二氯甲烷中混合约1小时。如果游离酸含有自由的羟基基团,如对-羟基苯基丙酸,则用额外的3摩尔当量的HOBT进行偶联。
[0981]可按照下列步骤测定本发明的化合物作为GLP-1结合化合物的活性。
细胞培养:
[0982]将表达GLP-1受体的RIN 5F大鼠胰岛瘤细胞(ATCC-#CRL-2058,American Type Culture Colletion,Manassas,VA)在含10%胎牛血清的Dulbecco’s改进的Eagle培养基(DMEM)中培养,并保持在约37℃下5%CO2/95%空气的湿润环境中。
放射性配体结合:
[0983]采用Brinkman Polytron(Westbury,NY)(设为6、15秒),通过RIN细胞在20ml冰冷的50mM Tris-HCl中的均化来制备用于放射性配体结合研究的膜。通过离心(39,000g/10分钟)洗涤匀浆两次,将最终的颗粒状物再悬浮于含2.5mM的MgCl2、0.1mg/ml杆菌肽(Sigma Chemical,St.Louis,MO)和0.1%BSA的50mM Tris-HCl中。为了测定,用含有或不含0.05ml未标记竞争试验肽的0.05nM[125I]GLP-1(7-36)(~2200Ci/mmol,NewEngland Nuclear,Boston,MA)孵育等分试样(0.4ml)。孵育100分钟(25℃)后,通过GF/C滤纸(Brandel,Gaithersburg,MD)的快速过滤从自由部分分离出结合的[125I]GLP-1(7-36)(SEQ ID NO:151),该滤纸之前在0.5%聚乙烯亚胺中浸湿。然后用冰冷的50mM Tris-HCl的5ml等分试样洗涤滤纸三次,通过γ光谱测定法(Wallac LKB,Gaithersburg,MD)计算残留在滤纸上的结合放射性。将特异性结合定义为总[125I]GLP-1(7-36)(SEQ ID NO:151)结合减去1000nM GLP1(7-36)(SEQ ID NO:3)存在下的结合(Bachem,Torrence,CA)。
[0984]本发明肽可以是药学上可接受的盐的形式。这些盐例如包括但不限于:与有机酸(例如醋酸、乳酸、马来酸、柠檬酸、苹果酸、抗坏血酸、琥珀酸、苯甲酸、甲磺酸、甲苯磺酸或扑酸(pamoic acid))形成的盐,与无机酸(例如盐酸、硫酸、或磷酸)形成的盐,和与聚合酸(例如鞣酸、羧甲基纤维素、聚乳酸、聚乙醇酸、或聚乳酸-聚乙醇酸的共聚物)形成的盐。制备本发明肽的盐的典型方法在本领域是公知的,它可通过标准的盐交换法来完成。因此,可以将本发明肽的TFA盐(TFA盐采用用含TFA的缓冲溶液洗脱的制备性HPLC对肽进行纯化而得到)转化成另一种盐,例如通过将肽溶解在少量0.25N醋酸水溶液中得到醋酸盐。将所得到的溶液装载到半制备性HPLC柱(Zorbax,300SB,C-8)中。用下列溶液洗脱该柱:(1)0.1N醋酸铵水溶液,0.5小时,(2)0.25N醋酸水溶液,0.5小时,和(3)流速为4ml/分钟的线性梯度(在30分钟内溶液B从20%变化到100%)(溶液A为0.25N醋酸水溶液;溶液B为80∶20的乙腈/水中的0.25N醋酸)。收集含肽的部分并冷冻至干。
[0985]如本领域技术人员所公知的,GLP-1已知的和潜在的用途是各种各样的(参见Todd,J.F.等,Clinical Science,1998,95,pp.325-329;以及Todd,J.F.等,European Journal of Clinical Investigation,1997,27,pp.533-536)。因此,施用本发明化合物来引起激动剂作用与GLP-1本身具有相同的效果和用途。可以将GLP-1的这些各种各样的用途总结如下:治疗I型糖尿病、H型糖尿病、肥胖症、胰高血糖素瘤、气管分泌性疾病、代谢性疾病、关节炎、骨质疏松症、中枢神经系统疾病、再狭窄、神经变性疾病、肾脏衰竭、充血性心力衰竭、肾病综合症、肝硬化、肺水肿、高血压和需要减少饮食摄入的疾病。引起患者激动剂作用的本发明的GLP-1类似物可用于治疗下列疾病:低血糖以及与胃切除术和小肠切除术有关的吸收障碍综合症。
[0986]因此,本发明的范围内包括了药物组合物,该药物组合物包括一种活性成分、至少一种式(I)化合物以及一种药学上可接受的载体。
[0987]本发明组合物中活性成分的剂量可以不同;但是,活性成分的量必须能获得适当的剂型。所选择的剂量根据所需治疗效果、给药途径和治疗周期而改变。一般来说,本发明活性成分的有效量为1×10-7-200mg/kg/天,优选1×10-4-100mg/kg/天,可以单剂量给药或分成多剂量给药。
[0988]本发明化合物可以经口服、非肠道(如肌内、腹膜内、静脉内、或皮下注射、或植入)、鼻腔、阴道、直肠、舌下或局部的给药途径进行给药,并可与药学上可接受的载体进行配制以提供适合于每一种给药途径的剂型。
[0989]口服的固体剂型包括胶囊、片剂、丸剂、粉剂和颗粒剂。在这些固体剂型中,将活性化合物与至少一种药学上可接受的惰性载体混合,该载体例如为蔗糖、乳糖、或淀粉。这些剂型作为正常使用也可包括除惰性稀释剂外的其它物质,例如,润滑剂(如硬脂酸镁)。在胶囊、片剂和丸剂的情况下,这些剂型也可包括缓冲剂。另外,片剂和丸剂可用肠衣制备。
[0990]口服的液体剂型包括药学上可接受的、含本领域通常使用的惰性稀释剂如水的乳剂、溶液、悬浮液、糖浆剂、酏剂。除了这些惰性稀释剂外,组合物也可包括辅剂,例如润湿剂、乳化剂、悬浮剂、甜味剂、调味剂和香料。
[0991]本发明用于非肠道给药的制剂包括无菌水溶液或非水溶液、悬浮液或乳剂。非水溶剂或赋形剂例如有丙二醇、聚乙二醇、植物油如橄榄油和玉米油、明胶、可注射的有机酯如油酸乙酯。这些剂型也可包含诸如防腐剂、润湿剂、乳化剂和分散剂之类的辅助剂。可以通过以下方法进行灭菌,例如经细菌存留过滤器过滤,在组合物中加入灭菌剂,照射组合物,或加热组合物。也可将它们制成无菌固体组合物的形式,在即将使用前将其溶解在无菌水、或一些其它可注射的无菌介质中。
[0992]直肠或阴道给药的组合物优选栓剂,除了活性物质外,它可包含赋形剂,例如可可脂或栓剂蜡。
[0993]也可用本领域公知的标准赋形剂制备鼻腔或舌下给药的组合物。
[0994]另外,本发明的化合物可以以持续释放组合物的形式给药,例如在下列专利和专利申请中所述:美国专利No.5,672,659教导了含生物活性剂和聚酯的持续释放组合物,美国专利No.5,595,760教导了含胶凝形式的生物活性剂的持续释放组合物,1997年9月9日提交的美国专利申请No.08/929,363教导了含生物活性剂和壳聚糖的聚合持续释放组合物,1996年11月1日提交的美国专利申请No.08/740,778公开了含生物活性剂和环糊精的持续释放组合物,1998年1月29日提交的美国专利申请09/015,394公开了含生物活性剂的可吸收持续释放组合物,1998年7月23日提交的美国专利申请No.09/121,653公开了一种在水包油过程中制备含诸如肽的治疗剂的微颗粒的方法,1998年8月10日提交的美国专利申请No.09/131,472公开了含诸如肽和磷酸化聚合物的治疗剂的复合体,1998年11月2日提交的美国专利申请No.09/184,413公开了含诸如肽和具有不可聚性内酯的聚合物的治疗剂的复合体。前述专利和申请的教导以引用方式并入本文。
[0995]除非另有说明,本文所用的所有技术和科学术语的含义与本发明所属领域的普通技术人员通常理解的相同。还有,本文提及的所有出版物、专利申请、专利和其它参考资料都以引用方式并入。
合成:
[0996]下列实施例描述了制备本发明肽的合成方法,这些方法对于本领域技术人员来说是众所周知的。在所涉及之处,试剂的用量约为以0.20mmol的规模进行合成的量。其它方法对于本领域技术人员来说也是公知的,因此,这些实施例的目的仅在于举例说明,而不是以任何方式限定本发明的范围。
[0997]各种各样的氨基酸,无论侧链是否受到保护,都可从多种商业来源获得。例如,下列的氨基酸(其中,当存在括号时,括号是指侧链保护基团)可不同地购自Bachem,Torrance,CA;Nova Biochem.,LaJolla,CA;Chem-Impex International;Wood Dale,IL;以及Synthetech,Inc.Albany,OR:Boc-Ado-OH,Boc-Aib-OH,Boc-Ala-OH,Boc-βAla-OH,Boc-Arg(Tos)-OH,Boc-D-Arg(Tos)-OH,Boc-Asp(OcHex)-OH,Boc-D-Asp(OcHex)-OH,Boc-Aun-OH,Boc-Ava-OH,Boc-Gln-OH,Boc-Glu(OcHex)-OH,Boc-Gly-OH,Boc-His(DNP)-OH,Boc-Ile-OH,Boc-Leu-OH,Boc-Lys(2ClZ)-OH,Boc-Nal-OH,Boc-Phe-OH,Boc-Ser(Bzl)-OH,Boc-Thr(Bzl)-OH,Boc-Trp(Fm)-OH,Boc-Tyr(2BrZ)-OH,以及Boc-Val-OH。
实施例1:(Ser3,Aib35)hGLP-1(7-36)NH2的合成
[0998]标题肽的合成可在进行加速Boc-化学固相肽合成的改进应用生物系统(Foster City,CA)430A型肽合成器上进行(参见Schnolzer等,Int.J.Peptide Protein Res.,90:180(1992).)。可采用具有0.91mmol/g取代物的4-甲基二苯甲胺(MBHA)树脂(Peninsula Laboratories,Belmont,CA)。可采用例如具有下列侧链保护的Boc氨基酸(Bachem,CA,Torrance,CA;Nova Biochem.,LaJolla,CA):Boc-Ala-OH,Boc-Arg(Tos)-OH,Boc-Asp(OcHex)-OH,Boc-Tyr(2BrZ)-OH,Boc-His(DNP)-OH,Boc-Val-OH,Boc-Leu-OH,Boc-Gly-OH,Boc-Gln-OH,Boc-Ile-OH,Boc-Lys(2ClZ)-OH,Boc-Thr(Bzl)-OH,Boc-Ser(Bzl)-OH,Boc-Phe-OH,Boc-Glu(OcHex)-OH以及Boc-Trp(Fm)-OH。通过用100%TFA处理2×1分钟,可除去Boc基团。用HBTU(2.0mmol)和DIEA(1.0mL)在4mL DMF中对Boc氨基酸(2.5mmol)进行预活化,并在末预先中和肽-树脂TFA盐的情况下进行偶联。
[0999]在肽链装配结束时,用溶于DMF的20%氢硫基乙醇/10%DIEA溶液处理树脂2×30分钟,以脱去His侧链上的DNP基团。然后通过用100%TFA处理2×2分钟而脱去N-末端的Boc基团。用DMF中的10%DIEA中和肽--树脂(1×1分钟)后,通过用15%乙醇胺/15%水/70%DMF的溶液处理2×30分钟以脱去侧链上的甲酰基基团。然后,用DMF和DCM洗涤肽-树脂,并在减压下干燥。在0℃下,通过在含1ml茴香醚和二硫苏糖醇(24mg)的10ml HF中搅拌肽-树脂约75分钟以进行最终的离解。通入氮流除去HF,用乙醚(6×10ml)洗涤残余物,并用4N HOAc(6×10ml)进行萃取。
[01000]在反相制备性高效液相色谱(HPLC)上用反相VYDACC18柱(Nest Group,Southborough,MA)纯化水提物中的肽混合物。用线性梯度(20%-50%溶液B,105分钟)以10ml/分钟的流速(溶液A=含0.1%TFA的水;溶液B=含0.1%TFA的乙腈)洗脱该柱。收集各级份并在分析性HPLC上检测。然后合并含纯化产物的那些级份并冻干。可采用电喷质谱仪(MS(ES))分析法检测最终产物的分子量。
实施例2-7
[01001]按照实施例中详述的步骤,但在肽装配期间以适当的氨基酸进行替代,也可制备下列肽。
实施例2:(Abu8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.768)
实施例3:(Val8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.769)
实施例4:(β-Ala8,35)hGLP-1(7-36)NH2; (SEQ ID NO.770)
实施例5:(Abu8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.771)
实施例6:(Val8,Aib35)hGLP-1(7-36)NH2;以及(SEQ ID NO.772)
实施例7:(β-Ala8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.773)
[01002]前述的每一个实施例都可按照本文上述的步骤实施,而只需在肽装配期间在起始材料中采用合适的替代物。
其它实施方式
[01003]从以上的说明书出发,本领域的技术人员可容易地确定本发明的必要特征而在不偏离本发明的精神和范围的前提下对本发明作出各种变化和修饰,以适应于不同的用途和条件。因此,其它的实施方式也落在权利要求的范围内。
Claims (21)
1.通式(I)的化合物或其药学上可接受的盐,
(R2R3)-A7-A8-A9-A10-A11-A12-A13-A14-A15-A16-A17-A18-A19-A20-A21-A22-A23-A24-A25-A26-A27-A28-A29-A30-A31-A32-A33-A34-A35-A36-A37-A38-A39-R1,
(I)
其中:
A7是L-His,Ura,Paa,Pta,Amp,Tma-His,去氨基-His,或不存在;
A8是Abu,β-Ala,Ser,Gly或Val;
A9是Glu,N-Me-Glu,N-Me-Asp或Asp;
A10是Gly,Acc,β-Ala或Aib;
A11是Thr或Ser;
A12是Phe,Acc,Aic,Aib,3-Pal,4-Pal,1-Nal,2-Nal,Cha,Trp或X1-Phe;
A13是Thr或Ser;
A14是Ser或Aib;
A15是Asp或Glu;
A16是Val,Acc,Aib,Leu,Ile,Tle,Nle,Abu,Ala或Cha;
A17是Ser或Thr;
A18是Ser或Thr;
A19是Tyr,Cha,Phe,3-Pal,4-Pal,Acc,1-Nal,2-Nal或X1-Phe;
A20是Leu,Acc,Aib,Nle,Ile,Cha,Tle,Val,Phe或X1-Phe;
A21是Glu或Asp;
A22是Gly,Acc,β-Ala,Glu或Aib;
A23是Gln,Asp,Asn或Glu;
A24是Ala,Aib,Val,Abu,Tle或Acc;
A25是Ala,Aib,Val,Abu,Tle,Acc,Lys,Arg,hArg,Orn,HN-CH((CH2)n-N(R10R11))-C(O)或HN-CH((CH2)e-X3)-C(O);
A26是Lys,Arg,hArg,Orn,HN-CH((CH2)n-N(R10R11))-C(O)或HN-CH((CH2)e-X3)-C(O);
A27是Glu,Asp,Leu,Aib或Lys;
A28是Phe,3-Pal,4-Pal,1-Nal,2-Nal,X1-Phe,Aic,Acc,Aib,Cha或Trp;
A29是Ile,Acc,Aib,Leu,Nle,Cha,Tle,Val,Abu,Ala或Phe;
A30是Ala,Aib或Acc;
A31是Trp,1-Nal,2-Nal,3-Pal,4-Pal,Phe,Acc,Aib或Cha;
A32是Leu,Acc,Aib,Nle,Ile,Cha,Tle,Phe,X1-Phe或Ala;
A33是Val,Acc,Aib,Leu,Ile,Tle,Nle,Cha,Ala,Phe,Abu,Lys或X1-Phe;
A34是Lys,Arg,hArg,Orn,HN-CH((CH2)n-N(R10R11))-C(O)或HN-CH((CH2)e-X3)-C(O);
A35是Gly,β-Ala,D-Ala,Gaba,Ava,HN-(CH2)m-C(O),Aib,Acc或D-氨基酸;
A36是L-或D-Arg,D-或L-Lys,D-或L-hArg,D-或L-Orn,HN-CH((CH2)n-N(R10R11))-C(O),HN-CH((CH2)e-X3)-C(O)或不存在;
A37是Gly,β-Ala,Gaba,Ava,Aib,Acc,Ado,Arg,Asp,Aun,Aec,HN-(CH2)m-C(O),HN-CH((CH2)n-N(R10R11))-C(O),HN-CH((CH2)n-O(R10))-C(O),D-氨基酸或不存在;
A38是D-或L-Lys,D-或L-Arg,D-或L-hArg,D-或L-Orn,HN-CH((CH2)n-N(R10R11))-C(O),HN-CH((CH2)e-X3)-C(O)Ava,Ado,Aec或不存在;
A39是D-或L-Lys,D-或L-Arg,HN-CH((CH2)n-N(R10R11))-C(O),Ava,Ado,Aec,或Aun,或不存在;
每一次出现的X1独立地选自由(C1-C6)烷基,OH和卤素构成的组中;
R1是OH,NH2,(C1-C30)烷氧基,或NH-X2-CH2-Z0,其中X2是(C1-C12)烃基部分,以及Z0是H,OH,CO2H或CONH2;
R2和R3各自独立地选自由H,(C1-C30)烷基,(C2-C30)烯基,苯基(C1-C30)烷基,萘基(C1-C30)烷基,羟基(C1-C30)烷基,羟基(C2-C30)烯基,羟基苯基(C1-C30)烷基,以及羟基萘基(C1-C30)烷基构成的组中;或R2和R3其中之一是(C1-C30)酰基,(C1-C30)烷基磺酰基,C(O)X5,或
其中Y是H,OH或NH2;r是0-4;q是0-4;以及X5是(C1-C30)烷基,(C2-C30)烯基,苯基(C1-C30)烷基,萘基(C1-C30)烷基,羟基(C1-C30)烷基,羟基(C2-C30)烯基,羟基苯基(C1-C30)烷基或羟基萘基(C1-C30)烷基;
每一次独立出现的e独立地为1-4的整数;
每一次独立出现的m独立地为5-24的整数;
每一次独立出现的n独立地为1-5的整数;
每一次独立出现的R10和R11各自独立地为H,(C1-C30)烷基,(C1-C30)酰基,(C1-C30)烷基磺酰基,-C((NH)(NH2))或
以及
每一次出现的R12和R13各自独立地为(C1-C30)烷基;
条件是:
(i)所述的化合物不是:
(Ser8,β-Ala35)hGLP-1(7-36)NH2(SEQ ID NO.779);
(Gly8,Aib35)hGLP-1(7-36)NH2(SEQ ID NO.780);或
(Gly8,β-Ala35)hGLP-1(7-36)NH2(SEQ ID NO.781);
(ii)当A7是Ura,Paa或Pta时,则R2和R3不存在;以及
(iii)当R10是(C1-C30)酰基,(C1-C30)烷基磺酰基,-C((NH)(NH2))或时,则R11是H或(C1-C30)烷基。
2.根据权利要求1所述的化合物或其药学上可接受的盐,其中,A11是Thr;A13是Thr;A15是Asp;A17是Ser;A18是Ser;A21是Glu;A23是Gln或Glu;A27是Glu;以及A31是Trp。
3.根据权利要求2所述的化合物或其药学上可接受的盐,其中,A9是Glu,N-Me-Glu或N-Me-Asp;A12是Phe,Acc或Aic;A16是Val,Acc或Aib;A19是Tyr;A20是Leu,Acc或Cha;A24是Ala,Aib或Acc;A25是Ala,Aib,Acc,Lys,Arg,hArg,Orn,HN-CH((CH2)n-N(R10R11))-C(O)或HN-CH((CH2)e-X3)-C(O);A28是Phe;A29是Ile或Acc;A30是Ala或Aib;A32是Leu,Acc或Cha;以及A33是Val或Acc。
4.根据权利要求3所述的化合物或其药学上可接受的盐,其中,A10是Gly;A12是Phe,A6c或A5c;A16是Val,A6c或A5c;A20是Leu,A6c,A5c或Cha;A22是Gly,β-Ala或Aib;A24是Ala或Aib;A29是Ile,A6c或A5c;A32是Leu,A6c,A5c或Cha;A33是Val,A6c或A5c;A35是Aib,β-Ala,Ado,A6c,A5c或Gly;以及A37是Gly,Aib,β-Ala,Ado,D-Ala或不存在。
5.根据权利要求4所述的化合物或其药学上可接受的盐,其中,每次出现的X4是-C(O)-;每次出现的e为1或2;以及R1为OH或NH2X4。
9.根据权利要求5所述的化合物或其药学上可接受的盐,其中,其中,A8是Gly,Ser或Val。
10.根据权利要求9所述的化合物或其药学上可接受的盐,其中,A8是Gly或Ser。
11.根据权利要求10所述的化合物或其药学上可接受的盐,其中,所述化合物具有下列结构式:
((Nα-Me-His)7,Gly8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.1)
((Nα-Me-His)7,Gly8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.2)
((Nα-Me-His)7,Gly8,Aib35,Arg26,34)hGLP-1(7-36)NH2; (SEQ ID NO.3)
((Nα-Me-His)7,Gly8,Arg26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.4)
(Gly8,A6c35)hGLP-1(7-36)NH2; (SEQ ID NO.5)
(Gly8,A5c35)hGLP-1(7-36)NH2; (SEQ ID NO.6)
(Gly8,D-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.7)
(Gly8,Aib35,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.8)
(Gly8,Aib35,A5c32)hGLP-1(7-36)NH2; (SEQ ID NO.9)
(Gly8,Aib35,Glu23)hGLP-1(7-36)NH2; (SEQ ID NO.10)
(Gly8,Aib24,35)hGLP-1(7-36)NH2; (SEQ ID NO.11)
(Gly8,Aib30,35)hGLP-1(7-36)NH2; (SEQ ID NO.12)
(Gly8,Aib25,35)hGLP-1(7-36)NH2; (SEQ ID NO.13)
(Gly8,Aib35,A6c16,20)hGLP-1(7-36)NH2; (SEQ ID NO.14)
(Gly8,Aib35,A6c16,29,32)hGLP-1(7-36)NH2; (SEQ ID NO.15)
(Gly8,Aib35,A6c20,32)hGLP-1(7-36)NH2; (SEQ ID NO.16)
(Gly8,Aib35,A6c20)hGLP-1(7-36)NH2; (SEQ ID NO.17)
(Gly8,Aib35,Lys25)hGLP-1(7-36)NH2; (SEQ ID NO.18)
(Gly8,Aib24,35,A6c20)hGLP-1(7-36)NH2; (SEQ ID NO.19)
(Gly8,Aib35,A6c29,32)hGLP-1(7-36)NH2; (SEQ ID NO.20)
(Gly8,Aib24,35,A6c29,32)hGLP-1(7-36)NH2; (SEQ ID NO.21)
(Gly8,Aib35,A6c12)hGLP-1(7-36)NH2; (SEQ ID NO.22)
(Gly8,Aib35,Cha20)hGLP-1(7-36)NH2; (SEQ ID NO.23)
(Gly8,Aib35,A6c33)hGLP-1(7-36)NH2; (SEQ ID NO.24)
(Gly8,A6c16,20,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.25)
(Gly8,Aib35,β-Ala22)hGLP-1(7-36)NH2; (SEQ ID NO.26)
(Gly8,Aib22,35)hGLP-1(7-36)NH2; (SEQ ID NO.27)
(Gly8,Aib35,Glu23,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.28)
(Gly8,Aib24,35,Glu23,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.29)
(Gly8,Aib24,25,35,Glu23,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.30)
(Gly8,Aib24,25,35,A6c18,20,32,Glu23)hGLP-1(7-36)NH2; (SEQ ID NO.31)
(Gly8,A6c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.32)
(Gly8,A5c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.33)
(Gly8,Glu23,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.34)
(Gly8,Aib24,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.35)
(Gly8,Aib30,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.36)
(Gly8,Aib25,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.37)
(Gly8,A6c16,29,32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.38)
(Gly8,A6c20,32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.39)
(Gly8,A6c20,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.40)
(Gly8,Lys25,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.41)
(Gly8,Aib24,A6c20,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.42)
(Gly8,A6c29,32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.43)
(Gly8,Aib24,A6c29,32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.44)
(Gly8,A6c12,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.45)
(Gly8,Cha20,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.46)
(Gly8,A6c33,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.47)
(Gly8,β-Ala22,35)hGLP-1(7-36)NH2; (SEQ ID NO.48)
(Gly8,Aib22,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.49)
(Gly8,Glu23,A6c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.50)
(Gly8,Aib24,Glu23,A6c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.51)
(Gly8,Aib24,Glu23,A6c32,Lys34(Ne-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.52)
(Gly8,Aib24,25,Glu23,A6c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.53)
(Gly8,Aib24,25,A6c16,20,32,Glu23,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.54)
(Gly8,Aib35,D-Arg36)hGLP-1(7-36)NH2; (SEQ ID NO.55)
(Gly8,Aib35,D-Lys36)hGLP-1(7-36)NH2; (SEQ ID NO.56)
(Gly8,β-Ala35,D-Arg36)hGLP-1(7-36)NH2; (SEQ ID NO.57)
(Gly8,β-Ala35,D-Lys36)hGLP-1(7-36)NH2; (SEQ ID NO.58)
(Gly8,Aib35,Arg26,34)hGLP-1(7-36)NH2; (SEQ ID NO.59)
(Gly8,Arg26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.60)
(Gly8,Aib35,Arg25,26,34)hGLP-1(7-36)NH2; (SEQ ID NO.61)
(Gly8,Arg25,26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.62)
(Gly8,Arg26,34,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)OH; (SEQ ID NO.63)
(Gly8,Aib35,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-37)OH; (SEQ ID NO.64)
(Gly8,Aib35,37,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-37)OH; (SEQ ID NO.65)
(Gly8,Aib35,Arg26,34,Lys36(Nε-十四烷酰基),D-Ala37)hGLP-1(7-37)OH; (SEQ ID NO.66)
(Gly8,Aib35,37,Arg26,34,Lys38(Nε-十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.67)
(Gly8,Aib35,Arg26,34,β-Ala37,Lys38(Nε-十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.68)
(Gly8,Aib35,Arg26,34,Lys38(Nε-十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.69)
(Gly8,Arg26,34,Lys36(Nε-十四烷酰基),β-Ala37)hGLP-1(7-37)OH; (SEQ ID NO.70)
(Gly8,Aib37,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-37)OH; (SEQ ID NO.71)
(Gly8,Aib35,Arg26,34,Ado37)hGLP-1(7-37)OH; (SEQ ID NO.72)
(Gly8,Aib35,Arg26,34,Ado37)hGLP-1(7-37)NH2; (SEQ ID NO.73)
(Gly8,Arg26,34,Lys36(Nε-十四烷酰基),D-Ala37)hGLP-1(7-37)OH; (SEQ ID NO.74)
(Gly8,Aib37,Arg26,34,Lys38(Nε-十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.75)
(Gly8,Arg26,34,β-Ala37,Lys38(Nε-十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.76)
(Gly8,Aib35,Lys26(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.77)
(Gly8,Aib35,Lys26(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.78)
(Gly8,Aib35,Lys26(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.79)
(Gly8,Lys26(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.80)
(Gly8,Lys26(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.81)
(Gly8,Lys26(Nε-十六烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.82)
(Gly8,Aib35,Lys26(Nε-辛酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.83)
(Gly8,Aib35,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.84)
(Gly8,Aib35,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.85)
(Gly8,Aib35,Lys26(Nε-癸酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.86)
(Gly8,Aib35,Lys25,Lys26(Nε-辛酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.87)
(Gly8,Aib35,Lys25,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.88)
(Gly8,Aib35,Lys25,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.89)
(Gly8,Aib35,Arg25,34,Lys26(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.90)
(Gly8,Aib35,Arg25,34,Lys26(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.91)
(Gly8,Aib35,Arg25,34,Lys26(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.92)
(Gly8,Aib35,Arg25,34,Lys26(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.93)
(Gly8,Lys26(Nε-辛酰基),Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.94)
(Gly8,Lys26(Nε-十四烷酰基),Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.95)
(Gly8,Lys26(Nε-十六烷酰基),Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.96)
(Gly8,Lys26(Nε-癸酰基),Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.97)
(Gly8,Aib35,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.98)
(Gly8,Aib35,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.99)
(Gly8,Aib35,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.100)
(Gly8,Aib35,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.101)
(Gly8,Aib35,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.102)
(Gly8,Aib35,Arg26,Lys34(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.103)
(Gly8,Aib35,Arg25,26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.104)
(Gly8,Aib35,Arg25,26,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.105)
(Gly8,Aib35,Arg25,26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.106)
(Gly8,Aib35,Arg25,26,Lys34(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.107)
(Gly8,Aib35,Lys25,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.108)
(Gly8,Aib35,Lys25,Arg26,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.109)
(Gly8,Aib35,Lys25,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.110)
(Gly8,Aib35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.111)
(Gly8,Aib35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.112)
(Gly8,Aib35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.113)
(Gly8,Aib35,Arg26,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.114)
(Gly8,Aib35,Arg26,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.115)
(Gly8,Aib35,Arg26,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.116)
(Gly8,Aib35,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.117)
(Gly8,Aib35,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2 (SEQ ID NO.118)
(Gly8,Aib35,Arg26,34,Lys38(Nε-辛酰基))hGLP-1(7-38)NH2; (SEQ ID NO.119)
(Gly8,Aib35,Arg26,34,Lys38(Nε-癸酰基))hGLP-1(7-38)NH2; (SEQ ID NO.120)
(Gly8,Aib35,Arg26,34,Lys38(Nε-十四烷酰基))hGLP-1(7-38)NH2; (SEQ ID NO.121)
(Gly8,Aib35,Arg26,34,Lys38(Nε-十六烷酰基))hGLP-1(7-38)NH2; (SEQ ID NO.122)
(Gly8,Aib35,37,Arg25,26,34,Lys38(Nε-辛酰基))hGLP-1(7-38)NH2; (SEQ ID NO.123)
(Gly8,Aib35,37,Arg25,26,34,Lys38(Nε-癸酰基))hGLP-1(7-38)NH2; (SEQ ID NO.124)
(Gly8,Aib35,37,Arg25,26,34,Lys38(Nε-十四烷酰基))hGLP-1(7-38)NH2; (SEQ ID NO.125)
(Gly8,Aib35,37,Arg25,26,34,Lys38(Nε-十六烷酰基)hGLP-1(7-38)NH2; (SEQ ID NO.126)
(Gly8,Aib35,37,Arg26,34,Lys38(Nε-辛酰基))hGLP-1(7-38)NH2; (SEQ ID NO.127)
(Gly8,Aib35,37,Arg26,34,Lys38(Nε-癸酰基))hGLP-1(7-38)NH2; (SEQ ID NO.128)
(Gly8,Aib35,37,Arg26,34,Lys38(Nε-十六烷酰基))hGLP-1(7-38)NH2; (SEQ ID NO.129)
(Gly8,Aib35,Lys25,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2;(SEQ ID NO.130)
(Gly8,Aib35,Lys25,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.131)
(Gly8,Aib35,Lys25,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.132)
(Gly8,Aib35,Arg25,26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.133)
(Gly8,Aib35,Arg25,26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.134)
(Gly8,Aib35,Arg25,26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.135)
(Gly8,Aib35,Arg25,26,34,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.136)
(Gly8,Lys34(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.137)
(Gly8,Lys34(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.138)
(Gly8,Lys34(Nε-十六烷酰基),β-Ala35)hGLP-11(7-36)NH2; (SEQ ID NO.139)
(Gly8,A6c32,Lys34(Ne-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.140)
(Gly8,Glu23,Lys34(Ne-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.141)
(Gly8,Glu23,A6c32,Lys34(Ne-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.142)
(Gly8,Arg26,Lys34(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.143)
(Gly8,Arg26,Lys34(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.144)
(Gly8,Arg26,Lys34(Nε-十六烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.145)
(Gly8,Arg26,Lys34(Nε-癸酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.146)
(Gly8,Arg25,26,Lys34(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.147)
(Gly8,Arg25,26,Lys34(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.148)
(Gly8,Arg25,26,Lys34(Nε-十六烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.149)
(Gly8,Arg25,26,Lys34(Nε-癸酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.150)
(Gly8,Lys25,Arg26,Lys34(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.151)
(Gly8,Lys25,Arg26,Lys34(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.152)
(Gly8,Lys25,Arg26,Lys34(Nε-十六烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.153)
(Gly8,β-Ala35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.154)
(Gly8,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.155)
(Gly8,β-Ala35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.156)
(Gly8,Arg26,β-Ala35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.157)
(Gly8,Arg26,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.158)
(Gly8,Arg26,β-Ala35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.159)
(Gly8,Arg26,34,β-Ala35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.160)
(Gly8,Arg26,34,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.161)
(Gly8,Arg26,34,β-Ala35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NQ.162)
(Gly8,Arg26,34,β-Ala35,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.163)
(Gly8,Lys25,Arg26,34,β-Ala35,Lys36(Nε-辛酰基-))hGLP-1(7-36)NH2; (SEQ ID NO.164)
(Gly8,Lys25,Arg26,34,Lys36(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.165)
(Gly8,Lys25,Arg26,34,β-Ala35,Lys36(Nε- (SEQ ID NO.166)
hexadecanoyl))hGLP-1(7-36)NH2;
(Gly8,Arg25,26,34,β-Ala35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.167)
(Gly8,Arg25,26,34,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.168)
(Gly8,Arg25,26,34,β-Ala35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.169)
(Gly8,Arg25,26,34,β-Ala35,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.170)
(Gly8,Aib35,Lys26(Nε-辛酰基),A6c32,Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.171)
(Gly8,Aib35,Lys26(Nε-十四烷酰基),A6c32,Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.172)
(Gly8,Aib35,Lys26(Nε-十六烷酰基),A6c32,Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.173)
(Gly8,Aib35,A6c32,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.174)
(Gly8,Aib35,A6c32,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.175)
(Gly8,Aib35,A6c32,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.176)
(Gly8,Aib35,Arg26,A6c32,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.177)
(Gly8,Aib35,Arg26,A6c32,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.178)
(Gly8,Aib35,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.179)
(Gly8,Aib35,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.180)
(Gly8,Aib35,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.181)
(Gly8,Aib35,Arg26,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.182)
(Gly8,Aib35,Arg26,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.183)
(Gly8,Aib35,Arg26,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.184)
(Gly8,Aib35,Arg26,34,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.185)
(Gly8,Aib35,Arg26,34,A6c32,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.186)
(Gly8,Aib35,Arg26,34,A6c32,Lys36(Nε- (SEQ ID NO.187)十四烷酰基))hGLP-1(7-36)NH2;
(Gly8,Aib35,Arg26,34,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.188)
(Gly8,Aib24,35,Lys26(Nε-octanoyl),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.189)
(Gly8,Aib24,35,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.190)
(Gly8,Aib24,35,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.191)
(Gly8,Aib24,35,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.192)
(Gly8,Aib24,35,Arg26,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.193)
(Gly8,Aib24,35,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.194)
(Gly8,Aib24,35,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.195)
(Gly8,Aib24,35,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.196)
(Gly8,Aib24,35,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.197)
(Gly8,Aib24,35,Glu23,A6c32,Lys34(Ne-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.198)
(Gly8,Aib35,Glu23,Lys26(Nε-辛酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.199)
(Gly8,Aib35,Glu23,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.200)
(Gly8,Aib35,Glu23,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.201)
(Gly8,Aib35,Glu23,Lys34(Ne-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.202)
(Gly8,Aib35,Glu23,A6c32,Lys34(Ne-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.203)
(Gly8,Aib35,Glu23,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.204)
(Gly8,Aib35,Glu23,Arg26,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.205)
(Gly8,Aib35,Glu23,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.206)
(Gly8,Aib35,Glu23,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.207)
(Gly8,Aib35,Glu23,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.208)
(Gly8,Aib35,Glu23,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.209)
(Gly8,Aib35,Glu23,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.210)
(Gly8,Aib35,Glu23,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.211)
(Gly8,Aib35,Glu23,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.212)
(Gly8,Aib30,35,Lys26(Nε-辛酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.213)
(Gly8,Aib30,35,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.214)
(Gly8,Aib30,35,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.215)
(Gly8,Aib30,35,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.216)
(Gly8,Aib30,35,Arg26,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.217)
(Gly8,Aib30,35,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.218)
(Gly8,Aib30,35,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.219)
(Gly8,Aib30,35,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.220)
(Gly8,Aib30,35,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.221)
(Gly8,Aib35,Glu23,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.222)
(Gly8,Aib35,Glu23,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.223)
(Gly8,Aib35,Glu23,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.224)
(Gly8,Aib35,Glu23,Arg26,34,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.225)
(Gly8,Aib35,Glu23,Arg26,34,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.226)
(Gly8,Aib35,Glu23,Arg26,34,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.227)
(Gly8,Aib24,35,Glu23,Arg26,34,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.228)
(Gly8,Aib24,35,Glu23,Arg26,34,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.229)
(Gly8,Aib24,35,Glu23,Arg26,34,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.230)
(Gly8,Aib24,30,35,Glu23,Arg26,34,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.231)
(Gly8,Aib24,30,35,Glu23,Arg26,34,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.232)
(Gly8,Aib24,30,35,Glu23,Arg26,34,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.233)
((Nα-HEPES-His)7,Gly8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.234)
((Nα-HEPA-His)7,Gly8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.235)
((Nα-十四烷酰基-His)7,Gly8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.236)
((Nα-十四烷酰基-His)7,Gly8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.237)
((Nα-十四烷酰基-His)7,Gly8,Aib35,Arg26,34)hGLP-1(7-36)NH2; (SEQ ID NO.238)
((Nα-十四烷酰基-His)7,Gly8,Arg26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NQ.239)
((Nα-十四烷酰基-His)7,Gly8,Aib35,Arg25,26,34)hGLP-1(7-36)NH2; (SEQ ID NO.240)
((Nα-十四烷酰基-His)7,Gly8,Arg25,26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.241)
(Gly8,Aib35,Lys26(Nε-辛烷磺酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.242)
(Gly8,Aib35,Lys26(Nε-十二烷磺酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.243)
(Gly8,Aib35,Lys26(Nε-十六烷磺酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.244)
(Gly8,Aib35,Arg26,Lys34(Nε-辛烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.245)
(Gly8,Aib35,Arg26,Lys34(Nε-十二烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.246)
(Gly8,Aib35,Arg26,Lys34(Nε-十六烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.247)
(Gly8,Aib35,Arg26,34,Lys36(Nε-辛烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.248)
(Gly8,Aib35,Arg26,34,Lys36(Nε-十六烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.249)
(Gly8,Aib35,Asp26(1-(4-癸基哌嗪)),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.250)
(Gly8,Aib35,Asp26(1-(4-十二烷基哌嗪)),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.251)
(Gly8,Aib35,Asp26(1-(4-十四烷基哌嗪)),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.252)
(Gly8,Aib35,Asp26(1-(4-十六烷基哌嗪)),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.253)
(Gly8,Aib35,Arg26,Asp34(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.254)
(Gly8,Aib35,Arg26,Asp34(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.255)
(Gly8,Aib35,Arg26,Asp34(1-(4-十四烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.256)
(Gly8,Aib35,Arg26,Asp34(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.257)
(Gly8,Aib35,Arg26,34,Asp36(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.258)
(Gly8,Aib35,Arg26,34,Asp36(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.259)
(Gly8,Aib35,Arg26,34,Asp36(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.260)
(Gly8,Aib35,Arg26,34,Asp38(1-(4-癸基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.261)
(Gly8,Aib35,Arg26,34,Asp38(1-(4-十二烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.262)
(Gly8,Aib35,Arg26,34,Asp38(1-(4-十四烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.263)
(Gly8,Aib35,Arg26,34,Asp38(1-(4-十六烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.264)
(Gly8,Aib35,37,Arg26,34,Asp38(1-(4-癸基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.265)
(Gly8,Aib35,37,Arg26,34,Asp38(1-(4-十二烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.266)
(Gly8,Aib35,37,Arg26,34,Asp38(1-(4-十四烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.267)
(Gly8,Aib35,37,Arg26,34,Asp38(1-(4-十六烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.268)
(Gly8,Aib35,Arg25,34,Asp26(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.269)
(Gly8,Aib35,Arg25,34,Asp26(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.270)
(Gly8,Aib35,Arg25,34,Asp26(1-(4-十四烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.271)
(Gly8,Aib35,Arg25,34,Asp26(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.272)
(Gly8,Aib35,Arg25,26,Asp34(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.273)
(Gly8,Aib35,Arg25,26,Asp34(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.274)
(Gly8,Aib35,Arg25,26,Asp34(1-(4-十四烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.275)
(Gly8,Aib35,Arg25,26,Asp34(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.276)
(Gly8,Aib35,Arg25,26,34,Asp36(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.277)
(Gly8,Aib35,Arg25,26,34,Asp36(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.278)
(Gly8,Aib35,Arg25,26,34,Asp36(1-(4-十四烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.279)
(Gly8,Aib35,Arg25,26,34,Asp36(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.280)
(Gly8,Aib35,Arg25,26,34,Asp38(1-(4-癸基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.281)
(Gly8,Aib35,Arg25,26,34,Asp38(1-(4- (SEQ ID NO.282)十二烷基哌嗪)))hGLP-1(7-38)NH2;
(Gly8,Aib35,Arg25,26,34,Asp38(1-(4-十四烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.283)
(Gly8,Aib35,Arg25,26,34,Asp38(1-(4-十六烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.284)
(Gly8,Aib35,37,Arg25,26,34,Asp38(1-(4-癸基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.285)
(Gly8,Aib35,37,Arg25,26,34,Asp38(1-(4-十二烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.286)
(Gly8,Aib35,37,Arg25,26,34,Asp38(1-(4-十四烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.287)
(Gly8,Aib35,37,Arg25,26,34,Asp38(1-(4-十六烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.288)
(Gly8,Aib35,Arg26,34,Glu36(1-十二烷基氨基))hGLP-1(7-36)NH2; (SEQ ID NO.289)
(Gly8,Aib35,Glu26(1-十二烷基氨基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.290)
(Gly8,Aib35,Arg26,Glu34(1-十二烷基氨基))hGLP-1(7-36)NH2; (SEQ ID NO.291)
(Gly8,Aib35,37,Arg26,34,Glu38(1-十二烷基氨围)hGLP-1(7-38)NH2;(SEQ ID NO.292)
(Gly8,Aib35,Arg34,Lys26(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.293)
(Gly8,Aib35,Arg34,Lys26(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.294)
(Gly8,Aib35,Arg34,Lys26(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.295)
(Gly8,Aib35,Arg34,Lys26(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.296)
(Gly8,Aib35,Arg26,Lys34(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.297)
(Gly8,Aib35,Arg26,Lys34(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.298)
(Gly8,Aib35,Arg26,Lys34(Nε-(2-(4-十四烷基-1-哌嗪)- (SEQ ID NO.299)乙酰基)))hGLP-1(7-36)NH2;
(Gly8,Aib35,Arg26,Lys34(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.300)
(Gly8,Aib35,Arg26,34,Lys36(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.301)
(Gly8,Aib35,Arg26,34,Lys36(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.302)
(Gly8,Aib35,Arg26,34,Lys36(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.303)
(Gly8,Aib35,Arg26,34,Lys38(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.304)
(Gly8,Aib35,Arg26,34,Lys38(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.305)
(Gly8,Aib35,Arg26,34,Lys38(Nε-(2-(4-十四完基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.306)
(Gly8,Aib35,Arg26,34,Lys38(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.307)
(Gly8,Aib35,37,Arg26,34,Lys38(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.308)
(Gly8,Aib35,37,Arg26,34,Lys38(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.309)
(Gly8,Aib35,37,Arg26,34,Lys38(Nε-(2-(4-十四完基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.310)
(Gly8,Aib35,37,Arg26,34,Lys38(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.311)
(Gly8,Aib35,Arg25,34,Lys26(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.312)
(Gly8,Aib35,Arg25,34,Lys26(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.313)
(Gly8,Aib35,Arg25,34,Lys26(Nε-(2-(4-十四完基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.314)
(Gly8,Aib35,Arg25,34,Lys26(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.315)
(Gly8,Aib35,Arg25,26,Lys34(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.316)
(GIy8,Aib35,Arg25,26,Lys34(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.317)
(GIy8,Aib35,Arg25,26,Lys34(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.318)
(Gly8,Aib35,Arg25,26,Lys34(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.319)
(Gly8,Aib35,Arg25,26,34,Lys36(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.320)
(Gly8,Aib35,Arg25,26,34,Lys36(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.321)
(Gly8,Aib35,Arg25,26,34,Lys36(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.322)
(Gly8,Aib35,Arg25,26,34,Lys36(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.323)
(Gly8,Aib35,Arg25,26,34,Lys38(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.324)
(Gly8,Aib35,Arg25,26,34,Lys38(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.325)
(Gly8,Aib35,Arg25,26,34,Lys38(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.326)
(Gly8,Aib35,Arg25,26,34,Lys38(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.327)
(Gly8,Aib35,37,Arg25,26,34,Lys38(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.328)
(Gly8,Aib35,37,Arg25,26,34,Lys38(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.329)
(Gly8,Aib35,37,Arg25,26,34,Lys38(Nε-(2-(4-十四烷基-1-哌嗪)- (SEQ ID NO.330)乙酰基)))hGLP-1(7-38)NH2;
(Gly8,Aib35,37,Arg25,26,34,Lys38(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.331)
(Gly8,Aib35,Arg26,34,Lys36(Nε-癸酰基))hGLP-1(7-36)OH; (SEQ ID NO.332)
(Gly8,Aib35,Lys25,Arg26,34,Lys36(Nε-癸酰基))hGLP-1(7-36)OH; (SEQ ID NO.333)
(Gly8,Aib35,Arg26,34,Ava37,Ado38)hGLP-1(7-38)NH2; (SEQ ID NO.334)
(Gly8,Aib35,Arg26,34,Asp37,Ava38,Ado39)hGLP-1(7-39)NH2; (SEQ ID NO.335)
(Gly8,Aib35,Arg26,34,Aun37)hGLP-1(7-37)NH2; (SEQ ID NO.336)
(Gly8,Aib17,35)hGLP-1(7-36)NH2; (SEQ ID NO.337)
(Gly8,Arg26,34,β-Ala35,D-Asp37,Ava38,Aun39)hGLP-1(7-39)NH2; (SEQ ID NO.338)
(Gly8,Glu22,23,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.339)
(Gly8,Lys18,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.340)
(Gly8,Leu27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.341)
(Gly8,Lys33,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.342)
(Gly8,Lys18,Leu27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.343)
(Gly8,D-Arg36)hGLP-1(7-36)NH2; (SEQ ID NO.344)
(Gly8,β-Ala35,D-Arg37)hGLP-1(7-37)NH2; (SEQ ID NO.345)
(Gly8,Aib27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.346)
(Gly8,Aib27,β-Ala35,37,Arg38)hGLP-1(7-38)NH2; (SEQ ID NO.347)
(Gly8,Aib27,β-Ala35,37,Arg38,39)hGLP-1(7-39)NH2; (SEQ ID NO.348)
(Gly8,Lys18,27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.349)
(Gly8,Lys27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.350)
(Gly8,β-Ala35,Arg38)hGLP-1(7-38)NH2; (SEQ ID NO.351)
(Gly8,Arg26,34,β-Ala35,)hGLP-1(7-36)NH2; (SEQ ID NO.352)
(Gly8,D-Arg35)hGLP-1(7-36)NH2; (SEQ ID NO.353)
(Gly8,β-Ala35,Arg37)hGLP-1(7-37)NH2; (SEQ ID NO.354)
(Gly8,Phe31,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.355)
(Gly8,Aib35,Phe31)hGLP-1(7-36)NH2; (SEQ ID NO.356)
(Gly8,Aib35,2-Nal31)hGLP-1(7-36)NH2; (SEQ ID NO.357)
(Gly8,Aib35,2-Nal28,31)hGLP-1(7-36)NH2; (SEQ ID NO.358)
(Gly8,Aib35,Arg26,34,2-Nal31)hGLP-1(7-36)NH2; (SEQ ID NO.359)
(Gly8,Aib35,Arg26,34,Phe31)hGLP-1(7-36)NH2; (SEQ ID NO.360)
(Gly8,Aib35,2-Nal19,31)hGLP-1(7-36)NH2; (SEQ ID NO.361)
(Gly8,Aib35,2-Nal12,31)hGLP-1(7-36)NH2; (SEQ ID NO.362)
(Gly8,Aib35,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.363)
(Gly8,Aib35,Arg34,Lys26(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.364)
(Gly8,Aib35,Arg26,34,Lys36(Nε-十二烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.365)
(Gly8,β-Ala35,Ser37(O-癸酰基))hGLP1(7-37)-NH2; (SEQ ID NO.366)
(Gly8,Aib27,β-Ala35,37,Arg38,Lys39(Nε-辛酰基))hGLP-1(7-39)NH2; (SEQ ID NO.367)
(Gly8,Arg26,34,β-Ala35,Lys37(Nε-辛酰基))hGLP-1(7-37)NH2; (SEQ ID NO.368)
(Gly8,Arg26,34,β-Ala35,Lys37(Nε-癸酰基))hGLP-1(7-37)NH2; (SEQ ID NO.369)
(Gly8,Arg26,34,β-Ala35,Lys37(Nε-十四烷酰基))hGLP-1(7-37)NH2; (SEQ ID NO.370)
(Gly8,Arg26,34,β-Ala35,Lys37(Nε-十二烷酰基))hGLP-1(7-37)NH2; (SEQ ID NO.371)
(Gly8,Arg26,34,β-Ala35,Lys37(Nε-十二烷酰基))hGLP-1(8-37)NH2; (SEQ ID NO.372)
(Gly8,Arg26,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.373)
(Gly8,Arg26,Phe31,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.374)
(Gly8,Arg26,Phe31,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.375)
(Gly8,Arg26,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.376)
(Gly8,Arg26,34,Phe31,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.377)
(Gly8,Arg26,34,Phe31,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.378)
(Gly8,Arg34,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.379)
(Gly8,Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.380)
(Gly8,Phe31,Arg34,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.381)
(Gly8,Phe31,Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.382)
(Gly8,Arg26,34,β-Ala35,Lys36(Nε-Aec-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.383)或(Gly8,β-Ala35,Ser37(O-癸酰基))hGLP1(7-37)-NH2; (SEQ ID NO.384)
12.根据权利要求10所述的化合物或其药学上可接受的盐,其中,所述化合物具有下列结构式:
((Nα-Me-His)7,Ser8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.385)
((Nα-Me-His)7,Ser8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.386)
((NαMe-His)7,Ser8,Aib35,Arg26,34)hGLP-1(7-36)NH2; (SEQ ID NO.387)
((Nα-Me-His)7,Ser8,Arg26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.388)
(Ser8,A6c35)hGLP-1(7-36)NH2; (SEQ ID NO.389)
(Ser8,A5c35)hGLP-1(7-36)NH2; (SEQ ID NO.390)
(Ser8,D-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.391)
(Ser8,Aib35,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.392)
(Ser8,Aib35,A5c32)hGLP-1(7-36)NH2; (SEQ ID NO.393)
(Ser8,Aib35,Glu23)hGLP-1(7-36)NH2; (SEQ ID NO.394)
(Ser8,Aib24,35)hGLP-1(7-36)NH2; (SEQ ID NO.395)
(Ser8,Aib30,35)hGLP-1(7-36)NH2; (SEQ ID NO.396)
(Ser8,Aib25,35)hGLP-1(7-36)NH2; (SEQ ID NO.397)
(Ser8,Aib35,A6c16,20)hGLP-1(7-36)NH2; (SEQ ID NO.398)
(Ser8,Aib35,A6c16,29,32)hGLP-1(7-36)NH2; (SEQ ID NO.399)
(Ser8,Aib35,A6c20,32)hGLP-1(7-36)NH2; (SEQ ID NO.400)
(Ser8,Aib35,A6c20)hGLP-1(7-36)NH2; (SEQ ID NO.401)
(Ser8,Aib35,Lys25)hGLP-1(7-36)NH2; (SEQ ID NO.402)
(Ser8,Aib24,35,A6c20)hGLP-1(7-36)NH2; (SEQ ID NO.403)
(Ser8,Aib35,A6c29,32)hGLP-1(7-36)NH2; (SEQ ID NO.404)
(Ser8,Aib24,35,A6c29,32)hGLP-1(7-36)NH2; (SEQ ID NO.405)
(Ser8,Aib35,A6c12)hGLP-1(7-36)NH2; (SEQ ID NO.406)
(Ser8,Aib35,Cha20)hGLP-1(7-36)NH2; (SEQ ID NO.407)
(Ser8,Aib35,A6c33)hGLP-1(7-36)NH2; (SEQ ID NO.408)
(Ser8,A6c16,20,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.409)
(Ser8,Aib35,β-Ala22)hGLP-1(7-36)NH2; (SEQ ID NO.410)
(Ser8,Aib22,35)hGLP-1(7-36)NH2; (SEQ ID NO.411)
(Ser8,Aib35,Glu23,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.412)
(Ser8,Aib24,35,Glu23,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.413)
(Ser8,Aib24,25,35,Glu23,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.414)
(Ser8,Aib24,25,35,A6c16,20,32,Glu23)hGLP-1(7-36)NH2; (SEQ ID NO.415)
(Ser8,A6c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.416)
(Ser8,A5c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.417)
(Ser8,Glu23,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.418)
(Ser8,Aib24,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.419)
(Ser8,Aib30,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.420)
(Ser8,Aib25,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.421)
(Ser8,A6c16,29,32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.422)
(Ser8,A6c20,32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.423)
(Ser8,A6c20,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.424)
(Ser8,Lys25,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.425)
(Ser8,Aib24,A6c20,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.426)
(Ser8,A6c29,32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.427)
(Ser8,Aib24,A6c29,32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.428)
(Ser8,A6c12,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.429)
(Ser8,Cha20,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.430)
(Ser8,A6c33,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.431)
(Ser8,β-Ala22,35)hGLP-1(7-36)NH2; (SEQ ID NO.432)
(Ser8,Alb22,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.433)
(Ser8,Glu23,A6c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.434)
(Ser8,Aib24,Glu23,A6c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.435)
(Ser8,Aib24,Glu23,A6c32,Lys34(Ne-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.436)
(Ser8,Aib24,25,Glu23,A6c32,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.437)
(Ser8,Aib24,25,A6c16,20,32,Glu23,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.438)
(Ser8,Aib35,D-Arg36)hGLP-1(7-36)NH2; (SEQ ID NO.439)
(Ser8,Aib35,D-Lys36)hGLP-1(7-36)NH2; (SEQ ID NO.440)
(Ser8,β-Ala35,D-Arg36)hGLP-1(7-36)NH2; (SEQ ID NO.441)
(Ser8,β-Ala35,D-Lys36)hGLP-1(7-36)NH2; (SEQ ID NO.442)
(Ser8,Aib35,Arg26,34)hGLP-1(7-36)NH2; (SEQ ID NO.443)
(Ser8,Arg26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.444)
(Ser8,Aib35,Arg25,26,34)hGLP-1(7-36)NH2; (SEQ ID NO.445)
(Ser8,Arg25,26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.446)
(Ser8,Arg26,34,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)OH; (SEQ ID NO.447)
(Ser8,Aib35,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-37)OH; (SEQ ID NO.448)
(Ser8,Aib35,37,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-37)OH; (SEQ ID NO.449)
(Ser8,Aib35,Arg26,34,Lys36(Nε-十四烷酰基),D-Ala37)hGLP-1(7-37)OH; (SEQ ID NO.450)
(Ser8,Aib35,37,Arg26,34,Lys38(Nε-十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.451)
(Ser8,Aib35,Arg26,34,β-Ala37,Lys38(Nε-十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.452)
(Ser8,Aib35,Arg26,34,Lys38(Nε-十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.453)
(Ser8,Arg26,34,Lys36(Nε-十四烷酰基),β-Ala37)hGLP-1(7-37)OH; (SEQ ID NO.454)
(Ser8,Aib37,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-37)OH; (SEQ ID NO.455)
(Ser8,Aib35,Arg26,34,Ado37)hGLP-1(7-37)OH; (SEQ ID NO.456)
(Ser8,Aib35,Arg26,34,Ado37)hGLP-1(7-37)NH2; (SEQ ID NO.457)
(Ser8,Arg26,34,Lys36(Nε-十四烷酰基),D-Ala37)hGLP-1(7-37)OH; (SEQ ID NO.458)
(Ser8,Aib37,Arg26,34,Lys38(Nε-十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.459)
(Ser8,Arg26,34,β-Ala37,Lys38(Nε-十四烷酰基))hGLP-1(7-38)OH; (SEQ ID NO.460)
(Ser8,Aib35,Lys26(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.461)
(Ser8,Aib35,Lys26(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.462)
(Ser8,Aib35,Lys26(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.463)
(Ser8,Lys26(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.464)
(Ser8,Lys26(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.465)
(Ser8,Lys26(Nε-十六烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.466)
(Ser8,Aib35,Lys26(Nε-辛酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.467)
(Ser8,Aib35,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.468)
(Ser8,Aib35,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.469)
(Ser8,Aib35,Lys26(Nε-癸酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.470)
(Ser8,Aib35,Lys25,Lys26(Nε-辛酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.471)
(Ser8,Aib35,Lys25,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.472)
(Ser8,Aib35,Lys25,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.473)
(Ser8,Aib35,Arg25,34,Lys26(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.474)
(Ser8,Aib35,Arg25,34,Lys26(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.475)
(Ser8,Aib35,Arg25,34,Lys26(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.476)
(Ser8,Aib35,Arg25,34,Lys26(Nε-decanoyl))hGLP-1(7-36)NH2; (SEQ ID NO.477)
(Ser8,Lys26(Nε-辛酰基),Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.478)
(Ser8,Lys26(Nε-十四烷酰基),Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.479)
(Ser8,Lys26(Nε-十六烷酰基),Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.480)
(Ser8,Lys26(Nε-癸酰基),Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.481)
(Ser8,Aib35,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.482)
(Ser8,Aib35,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.483)
(Ser8,Aib35,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.484)
(Ser8,Aib35,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.485)
(Ser8,Aib35,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.486)
(Ser8,Aib35,Arg26,Lys34(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.487)
(Ser8,Aib35,Arg25,26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.488)
(Ser8,Aib35,Arg25,26,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.489)
(Ser8,Aib35,Arg25,26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.490)
(Ser8,Aib35,Arg25,26,Lys34(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.491)
(Ser8,Aib35,Lys25,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.492)
(Ser8,Aib35,Lys25,Arg26,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.493)
(Ser8,Aib35,Lys25,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.494)
(Ser8,Aib35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.495)
(Ser8,Aib35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.496)
(Ser8,Aib35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.497)
(Ser8,Aib35,Arg26,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.498)
(Ser8,Aib35,Arg26,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.499)
(Ser8,Aib35,Arg26,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.500)
(Ser8,Aib35,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.501)
(Ser8,Aib35,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.502)
(Ser8,Aib35,Arg26,34,Lys38(Nε-辛酰基))hGLP-1(7-38)NH2; (SEQ ID NO.503)
(Ser8,Aib35,Arg26,34,Lys38(Nε-癸酰基))hGLP-1(7-38)NH2; (SEQ ID NO.504)
(Ser8,Aib35,Arg26,34,Lys38(Nε-十四烷酰基))hGLP-1(7-38)NH2; (SEQ ID NO.505)
(Ser8,Aib35,Arg26,34,Lys38(Nε-十六烷酰基))hGLP-1(7-38)NH2; (SEQ ID NO.506)
(Ser8,Aib35,37,Arg25,26,34,Lys38(Nε-辛酰基))hGLP-1(7-38)NH2; (SEQ ID NO.507)
(Ser8,Aib35,37,Arg25,26,34,Lys38(Nε-癸酰基))hGLP-1(7-38)NH2; (SEQ ID NO.508)
(Ser8,Aib35,37,Arg25,26,34,Lys38(Nε-十四烷酰基))hGLP-1(7-38)NH2; (SEQ ID NO.509)
(Ser8,Aib35,37,Arg25,26,34,Lys38(Nε-十六烷酰基))hGLP-1(7-38)NH2; (SEQ ID NO.510)
(Ser8,Aib35,37,Arg26,34,Lys38(Nε-辛酰基))hGLP-1(7-38)NH2; (SEQ ID NO.511)
(Ser8,Aib35,37,Arg26,34,Lys38(Nε-癸酰基))hGLP-1(7-38)NH2; (SEQ ID NO.512)
(Ser8,Aib35,37,Arg26,34,Lys38(Nε-十六烷酰基))hGLP-1(7-38)NH2; (SEQ ID NO.513)
(Ser8,Aib35,Lys25,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.514)
(Ser8,Aib35,Lys25,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.515)
(Ser8,Aib35,Lys25,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.516)
(Ser8,Aib35,Arg25,26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.517)
(Ser8,Aib35,Arg25,26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.518)
(Ser8,Aib35,Arg25,26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.519)
(Ser8,Aib35,Arg25,26,34,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.520)
(Ser8,Lys34(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.521)
(Ser8,Lys34(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.522)
(Ser8,Lys34(Nε-十六烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.523)
(Ser8,A6c32,Lys34(Ne-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.524)
(Ser8,Glu23,Lys34(Ne-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.525)
(Ser8,Glu23,A6c32,Lys34(Ne-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.526)
(Ser8,Arg26,Lys34(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.527)
(Ser8,Arg26,Lys34(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.528)
(Ser8,Arg26,Lys34(Nε-十六烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.529)
(Ser8,Arg26,Lys34(Nε-癸酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.530)
(Ser8,Arg25,26,Lys34(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.531)
(Ser8,Arg25,26,Lys34(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.532)
(Ser8,Arg25,26,Lys34(Nε-十六烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.533)
(Ser8,Arg25,26,Lys34(Nε癸酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.534)
(Ser8,Lys25,Arg26,Lys34(Nε-辛酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.535)
(Ser8,Lys25,Arg26,Lys34(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.536)
(Ser8,Lys25,Arg26,Lys34(Nε-十六烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.537)
(Ser8,β-Ala35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.538)
(Ser8,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.539)
(Ser8,β-Ala35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.540)
(Ser8,Arg26,β-Ala35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.541)
(Ser8,Arg26,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.542)
(Ser8,Arg26,β-Ala35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.543)
(Ser8,Arg26,34,β-Ala35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.544)
(Ser8,Arg26,34,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.545)
(Ser8,Arg26,34,β-Ala35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.546)
(Ser8,Arg26,34,β-Ala35,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.547)
(Ser8,Lys25,Arg26,34,β-Ala35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.548)
(Ser8,Lys25,Arg26,34,Lys36(Nε-十四烷酰基),β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.549)
(Ser8,Lys25,Arg26,34,β-Ala35,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.550)
(Ser8,Arg25,26,34,β-Ala35,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.551)
(Ser8,Arg25,26,34,β-Ala35,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.552)
(Ser8,Arg25,26,34,β-Ala35,Lys36(Nε- (SEQ ID NO.553)十六烷酰基))hGLP-1(7-36)NH2;
(Ser8,Arg25,26,34,β-Ala35,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.554)
(Ser8,Aib35,Lys26(Nε-辛酰基),A6c32,Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.555)
(Ser8,Aib35,Lys26(Nε-十四烷酰基),A6c32,Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.556)
(Ser8,Aib35,Lys26(Nε-十六烷酰基),A6c32,Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.557)
(Ser8,Aib35,A6c32,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.558)
(Ser8,Aib35,A6c32,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.559)
(Ser8,Aib35,A6c32,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.560)
(Ser8,Aib35,Arg26,A6c32,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.561)
(Ser8,Aib35,Arg26,A6c32,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.562)
(Ser8,Aib35,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.563)
(Ser8,Aib35,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.564)
(Ser8,Aib35,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.565)
(Ser8,Aib35,Arg26,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.566)
(Ser8,Aib35,Arg26,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.567)
(Ser8,Aib35,Arg26,A6c32,Lys36(Nε-hexadecanoyl))hGLP-1(7-36)NH2; (SEQ ID NO.568)
(Ser8,Aib35,Arg26,34,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.569)
(Ser8,Aib35,Arg26,34,A6c32,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.570)
(Ser8,Aib35,Arg26,34,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.571)
(Ser8,Aib35,Arg26,34,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.572)
(Ser8,Aib24,35,Lys26(Nε-辛酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.573)
(Ser8,Aib24,35,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.574)
(Ser8,Aib24,35,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.575)
(Ser8,Aib24,35,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.576)
(Ser8,Aib24,35,Arg26,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.577)
(Ser8,Aib24,35,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.578)
(Ser8,Aib24,35,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.579)
(Ser8,Aib24,35,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.580)
(Ser8,Aib24,35,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.581)
(Ser8,Aib24,35,Glu23,A6c32,Lys34(Ne-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.582)
(Ser8,Aib35,Glu23,Lys26(Nε-辛酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.583)
(Ser8,Aib35,Glu23,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.584)
(Ser8,Aib35,Glu23,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.585)
(Ser8,Aib35,Glu23,Lys34(Ne-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.586)
(Ser8,Aib35,Glu23,A6c32,Lys34(Ne-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.587)
(Ser8,Aib35,Glu23,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.588)
(Ser8,Aib35,Glu23,Arg26,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.589)
(Ser8,Aib35,Glu23,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.590)
(Ser8,Aib35,Glu23,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.591)
(Ser8,Aib35,Glu23,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.592)
(Ser8,Aib35,Glu23,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.593)
(Ser8,Aib35,Glu23,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.594)
(Ser8,Aib35,Glu23,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.595)
(Ser8,Aib35,Glu23,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.596)
(Ser8,Aib30,35,Lys26(Nε-辛酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.597)
(Ser8,Aib30,35,Lys26(Nε-十四烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.598)
(Ser8,Aib30,35,Lys26(Nε-十六烷酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.599)
(Ser8,Aib30,35,Arg26,Lys34(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.600)
(Ser8,Aib30,35,Arg26,Lys34(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.601)
(Ser8,Aib30,35,Arg26,Lys34(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.602)
(Ser8,Aib30,35,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.603)
(Ser8,Aib30,35,Arg26,34,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.604)
(Ser8,Aib30,35,Arg26,34,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.605)
(Ser8,Aib35,Glu23,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.606)
(Ser8,Aib35,Glu23,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.607)
(Ser8,Aib35,Glu23,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.608)
(Ser8,Aib35,Glu23,Arg26,34,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.609)
(Ser8,Aib35,Glu23,Arg26,34,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.610)
(Ser8,Aib35,Glu23,Arg26,34,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.611)
(Ser8,Aib24,35,Glu23,Arg26,34,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.612)
(Ser8,Aib24,35,Glu23,Arg26,34,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.613)
(Ser8,Aib24,35,Glu23,Arg26,34,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.614)
(Ser8,Aib24,30,35,Glu23,Arg26,34,A6c32,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.615)
(Ser8,Aib24,30,35,Glu23,Arg26,34,A6c32,Lys36(Nε-十四烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.616)
(Ser8,Aib24,30,35,Glu23,Arg26,34,A6c32,Lys36(Nε-十六烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.617)
((Nα-HEPES-His)7,Ser8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.618)
((Nα-HEPA-His)7,Ser8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.619)
((Nα-十四烷酰基-His)7,Ser8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.620)
((Nα-十四烷酰基-His)7,Ser8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.621)
((Nα-十四烷酰基-His)7,Ser8,Aib35,Arg26,34)hGLP-1(7-36)NH2; (SEQ ID NO.622)
((Nα-十四烷酰基-His)7,Ser8,Arg26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.623)
((Nα-十四烷酰基-His)7,Ser8,Aib35,Arg25,26,34)hGLP-1(7-36)NH2; (SEQ ID NO.624)
((Nα-十四烷酰基-His)7,Ser8,Arg25,26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.625)
(Ser8,Aib35,Lys26(Nε-辛烷磺酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.626)
(Ser8,Aib35,Lys26(Nε-十二烷磺酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.627)
(Ser8,Aib35,Lys26(Nε-十六烷磺酰基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.628)
(Ser8,Aib35,Arg26,Lys34(Nε-辛烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.629)
(Ser8,Aib35,Arg26,Lys34(Nε-十二烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.630)
(Ser8,Aib35,Arg26,Lys34(Nε-十六烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.631)
(Ser8,Aib35,Arg26,34,Lys36(Nε-辛烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.632)
(Ser8,Aib35,Arg26,34,Lys36(Nε-十六烷磺酰基))hGLP-1(7-36)NH2; (SEQ ID NO.633)
(Ser8,Aib35,Asp26(1-(4-癸基哌嗪)),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.634)
(Ser8,Aib35,Asp26(1-(4-十二烷基哌嗪)),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.635)
(Ser8,Aib35,Asp26(1-(4-十四烷基哌嗪)), (SEQ ID NO.636)Arg34)hGLP-1(7-36)NH2;
(Ser8,Aib35,Asp26(1-(4-十六烷基哌嗪)),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.637)
(Ser8,Aib35,Arg26,Asp34(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.638)
(Ser8,Aib35,Arg26,Asp34(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.639)
(Ser8,Aib35,Arg26,Asp34(1-(4-十四烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.640)
(Ser8,Aib35,Arg26,Asp34(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.641)
(Ser8,Aib35,Arg26,34,Asp36(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.642)
(Ser8,Aib35,Arg26,34,Asp36(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.643)
(Ser8,Aib35,Arg26,34,Asp36(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.644)
(Ser8,Aib35,Arg26,34,Asp38(1-(4-癸基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.645)
(Ser8,Aib35,Arg26,34,Asp38(1-(4-十二烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.646)
(Ser8,Aib35,Arg26,34,Asp38(1-(4-十四烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.647)
(Ser8,Aib35,Arg26,34,Asp38(1-(4-十六烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.648)
(Ser8,Aib35,37,Arg26,34,Asp38(1-(4-癸基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.649)
(Ser8,Aib35,37,Arg26,34,Asp38(1-(4-十二烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.650)
(Ser8,Aib35,37,Arg26,34,Asp38(1-(4-十四烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.651)
(Ser8,Aib35,37,Arg26,34,Asp38(1-(4-十六烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.652)
(Ser8,Aib35,Arg25,34,Asp26(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.653)
(Ser8,Aib35,Arg25,34,Asp26(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.654)
(Ser8,Aib35,Arg25,34,Asp26(1-(4-十四烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.655)
(Ser8,Aib35,Arg25,34,Asp26(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.656)
(Ser8,Aib35,Arg25,26,Asp34(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.657)
(Ser8,Aib35,Arg25,26,Asp34(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.658)
(Ser8,Aib35,Arg25,26,Asp34(1-(4-十四烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.659)
(Ser8,Aib35,Arg25,26,Asp34(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.660)
(Ser8,Aib35,Arg25,26,34,Asp36(1-(4-癸基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.661)
(Ser8,Aib35,Arg25,26,34,Asp36(1-(4-十二烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.662)
(Ser8,Aib35,Arg25,26,34,Asp36(1-(4-十四烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.663)
(Ser8,Aib35,Arg25,26,34,Asp36(1-(4-十六烷基哌嗪)))hGLP-1(7-36)NH2; (SEQ ID NO.664)
(Ser8,Aib35,Arg25,26,34,Asp38(1-(4-癸基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.665)
(Ser8,Aib35,Arg25,26,34,Asp38(1-(4-十二烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.666)
(Ser8,Aib35,Arg25,26,34,Asp38(1-(4- (SEQ ID NO.667)十四烷基哌嗪)))hGLP-1(7-38)NH2;
(Ser8,Aib35,Arg25,26,34,Asp38(1-(4-十六烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.668)
(Ser8,Aib35,37,Arg25,26,34,Asp38(1-(4-癸基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.669)
(Ser8,Aib35,37,Arg25,26,34,Asp38(1-(4-十二烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.670)
(Ser8,Aib35,37,Arg25,26,34,Asp38(1-(4-十四烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.671)
(Ser8,Aib35,37,Arg25,26,34,Asp38(1-(4-十六烷基哌嗪)))hGLP-1(7-38)NH2; (SEQ ID NO.672)
(Ser8,Aib35,Arg26,34,Glu36(1-十二烷基氨基))hGLP-1(7-36)NH2; (SEQ ID NO.673)
(Ser8,Aib35,Glu26(1-十二烷基氨基),Arg34)hGLP-1(7-36)NH2; (SEQ ID NO.674)
(Ser8,Aib35,Arg26,Glu34(1-十二烷基氨基))hGLP-1(7-36)NH2; (SEQ ID NO.675)
(Ser8,Aib35,37,Arg26,34,Glu38(1-十二烷基氨基))hGLP-1(7-38)NH2; (SEQ ID NO.676)
(Ser8,Aib35,Arg34,Lys26(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.677)
(Ser8,Aib35,Arg34,Lys26(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.678)
(Ser8,Aib35,Arg34,Lys26(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.679)
(Ser8,Aib35,Arg34,Lys26(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.680)
(Ser8,Aib35,Arg26,Lys34(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.681)
(Ser8,Aib35,Arg26,Lys34(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基))hGLP-1(7-36)NH2; (SEQ ID NO.682)
(Ser8,Aib35,Arg26,Lys34(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.683)
(Ser8,Aib35,Arg26,Lys34(Nε-(2-(4-十六烷基-1-哌嗪)- (SEQ ID NO.684)乙酰基)))hGLP-1(7-36)NH2;
(Ser8,Aib35,Arg26,34,Lys36(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.685)
(Ser8,Aib35,Arg26,34,Lys36(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.686)
(Ser8,Aib35,Arg26,34,Lys36(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.687)
(Ser8,Aib35,Arg26,34,Lys38(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.688)
(Ser8,Aib35,Arg26,34,Lys38(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.689)
(Ser8,Aib35,Arg26,34,Lys38(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.690)
(Ser8,Aib35,Arg26,34,Lys38(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.691)
(Ser8,Aib35,37,Arg26,34,Lys38(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.692)
(Ser8,Aib35,37,Arg26,34,Lys38(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.693)
(Ser8,Aib35,37,Arg26,34,Lys38(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.694)
(Ser8,Aib35,37,Arg26,34,Lys38(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.695)
(Ser8,Aib35,Arg25,34,Lys26(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.696)
(Ser8,Aib35,Arg25,34,Lys26(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.697)
(Ser8,Aib35,Arg25,34,Lys26(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.698)
(Ser8,Aib35,Arg25,34,Lys26(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.699)
(Ser8,Aib35,Arg25,26,Lys34(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.700)
(Ser8,Aib35,Arg25,26,Lys34(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.701)
(Ser8,Aib35,Arg25,26,Lys34(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.702)
(Ser8,Aib35,Arg25,26,Lys34(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.703)
(Ser8,Aib35,Arg25,26,34,Lys36(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.704)
(Ser8,Aib35,Arg25,26,34,Lys36(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.705)
(Ser8,Aib35,Arg25,26,34,Lys36(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.706)
(Ser8,Aib35,Arg25,26,34,Lys36(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-36)NH2; (SEQ ID NO.707)
(Ser8,Aib35,Arg25,26,34,Lys38(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.708)
(Ser8,Aib35,Arg25,26,34,Lys38(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.709)
(Ser8,Aib35,Arg25,26,34,Lys38(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.710)
(Ser8,Aib35,Arg25,26,34,Lys38(Nε-(2-(4-十六烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.711)
(Ser8,Aib35,37,Arg25,26,34,Lys38(Nε-(2-(4-癸基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.712)
(Ser8,Aib35,37,Arg25,26,34,Lys38(Nε-(2-(4-十二烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.713)
(Ser8,Aib35,37,Arg25,26,34,Lys38(Nε-(2-(4-十四烷基-1-哌嗪)-乙酰基)))hGLP-1(7-38)NH2; (SEQ ID NO.714)
(Ser8,Aib35,37,Arg25,26,34,Lys38(Nε-(2-(4-十六烷基-1-哌嗪)- (SEQ ID NO.715)乙酰基)))hGLP-1(7-38)NH2;
(Ser8,Aib35,Arg26,34,Lys36(Nε-癸酰基))hGLP-1(7-36)OH; (SEQ ID NO.716)
(Ser8,Aib35,Lys25,Arg26,34,Lys36(Nε-癸酰基))hGLP-1(7-36)OH; (SEQ ID NO.717)
(Ser8,Aib35,Arg26,34,Ava37,Ado38)hGLP-1(7-38)NH2; (SEQ ID NO.718)
(Ser8,Aib35,Arg26,34,Asp37,Ava38,Ado39)hGLP-1(7-39)NH2; (SEQ ID NO.719)
(Ser8,Aib35,Arg26,34,Aun37)hGLP-1(7-37)NH2; (SEQ ID NO.720)
(Ser8,Aib17,35,)hGLP-1(7-36)NH2; (SEQ ID NO.721)
(Ser8,Arg26,34,β-Ala35,D-Asp37,Ava38,Aun39)hGLP-1(7-39)NH2; (SEQ ID NO.722)
(Ser8,Glu22,23,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.723)
(Ser8,Lys18,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.724)
(Ser8,Leu27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.725)
(Ser8,Lys33,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.726)
(Ser8,Lys18,Leu27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.727)
(Ser8,D-Arg36)hGLP-1(7-36)NH2; (SEQ ID NO.728)
(Ser8,β-Ala35,D-Arg37)hGLP-1(7-37)NH2; (SEQ ID NO.729)
(Ser8,Aib27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.730)
(Ser8,Aib27,β-Ala35,37,Arg38)hGLP-1(7-38)NH2; (SEQ ID NO.731)
(Ser8,Aib27,β-Ala35,37,Arg38,39)hGLP-1(7-39)NH2; (SEQ ID NO.732)
(Ser8,Lys18,27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.733)
(Ser8,Lys27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.734)
(Ser8,β-Ala35,Arg38)hGLP-1(7-38)NH2; (SEQ ID NO.735)
(Ser8,Arg26,34,β-Ala35,)hGLP-1(7-36)NH2; (SEQ ID NO.736)
(Ser8,D-Arg35)hGLP-1(7-36)NH2; (SEQ ID NO.737)
(Ser8,β-Ala35,Arg37)hGLP-1(7-37)NH2; (SEQ ID NO.738)
(Ser8,Phe31,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.739)
(Ser8,Aib35,Phe31)hGLP-1(7-36)NH2; (SEQ ID NO.740)
(Ser8,Aib35,2-Nal31)hGLP-1(7-36)NH2; (SEQ ID NO.741)
(Ser8,Aib35,2-Nal28,31)hGLP-1(7-36)NH2; (SEQ ID NO.742)
(Ser8,Aib35,Arg26,34,2-Nal31)hGLP-1(7-36)NH2; (SEQ ID NO.743)
(Ser8,Aib35,Arg26,34,Phe31)hGLP-1(7-36)NH2; (SEQ ID NO.744)
(Ser8,Aib35,2-Nal19,31)hGLP-1(7-36)NH2; (SEQ ID NO.745)
(Ser8,Aib35,2-Nal12,31)hGLP-1(7-36)NH2; (SEQ ID NO.746)
(Ser8,Aib35,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.747)
(Ser8,Aib35,Arg34,Lys26(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.748)
(Ser8,Aib35,Arg26,34,Lys36(Nε-十二烷酰基))hGLP-1(7-36)NH2; (SEQ ID NO.749)
(Ser8,β-Ala35,Ser37(O-十二烷酰基))hGLP1(7-37)-NH2; (SEQ ID NO.750)
(Ser8,Aib27,β-Ala35,37,Arg38,Lys39(Nε-辛酰基))hGLP-1(7-3g)NH2; (SEQ ID NO.751)
(Ser8,Arg26,34,β-Ala35,Lys37(Nε-辛酰基))hGLP-1(7-37)NH2; (SEQ ID NO.752)
(Ser8,Arg26,34,β-Ala35,Lys37(Nε-癸酰基))hGLP-1(7-37)NH2; (SEQ ID NO.753)
(Ser8,Arg26,34,β-Ala35,Lys37(Nε-十四烷酰基))hGLP-1(7-37)NH2;(SEQ ID NO.754)
(Ser8,Arg26,34,β-Ala35,Lys37(Nε-十二烷酰基))hGLP-1(7-37)NH2;(SEQ ID NO.755)
(Ser8,Arg26,34,β-Ala35,Lys37(Nε-十二烷酰基))hGLP-1(8-37)NH2;(SEQ ID NO.756)
(Ser8,Arg26,34,β-Ala35,Lys36(Nε-Aec-癸酰基))hGLP-1(7-36)NH2;(SEQ ID NO.757)
(Ser8,Arg26,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.758)
(Ser8,Arg26,Phe31,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.759)
(Ser8,Arg26,Phe31,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.760)
(Ser8,Arg26,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.761)
(Ser8,Arg26,34,Phe31,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.762)
(Ser8,Arg34,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.763)
(Ser8,Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.764)
(Ser8,Phe31,Arg34,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.765)
or(Ser8,Phe31,Arg34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.766)
13.根据权利要求11所述的化合物或其药学上可接受的盐,其中,所述化合物是:
(Gly8,Aib35,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.8)
(Gly8,Aib35,Glu23)hGLP-1(7-36)NH2; (SEQ ID NO.10)
(Gly8,Aib24,35)hGLP-1(7-36)NH2; (SEQ ID NO.11)
(Gly8,Aib35,Glu23,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.28)
(Gly8,Glu23,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.34)
(Gly8,Aib35,Arg26,34)hGLP-1(7-36)NH2; (SEQ ID NO.59)
(Gly8,Aib35,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.117)
(Gly8,Aib35,Arg26,34,Lys36(Nε-癸酰基))hGLP-1(7-36)OH; (SEQ ID NO.332)
(Gly8,Aib35,Lys25,Arg26,34,Lys36(Nε-癸酰基))hGLP-1(7-36)OH; (SEQ ID NO.333)
(Gly8,Arg26,34,β-Ala35,Lys36(Nε-Aec-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.383)
(Gly8,Aib35,Arg26,34,Ava37,Ado38)hGLP-1(7-38)NH2; (SEQ ID NO.334)
(Gly8,Aib35,Arg26,34,A3p37,Ava38,Ado39)hGLP-1(7-39)NH2; (SEQ ID NO.335)
(Gly8,Aib35,Arg26,34,Aun37)hGLP-1(7-37)NH2; (SEQ ID NO.336)
(Gly8,Aib17,35)hGLP-1(7-36)NH2; (SEQ ID NO.337)
(Gly8,Arg26,34,β-Ala35,D-Asp37,Ava38,Aun39)hGLP-1(7-39)NH2;(SEQ ID NO.338)
(Gly8,Glu22,23,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.339)
(Gly8,Lys18,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.340)
(Gly8,Leu27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.341)
(Gly8,Lys33,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.342)
(Gly8,Lys18,Leu27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.343)
(Gly8,D-Arg36)hGLP-1(7-36)NH2; (SEQ ID NO.344)
(Gly8,β-Ala35,D-Arg37)hGLP-1(7-37)NH2; (SEQ ID NO.345)
(Gly8,Aib27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.346)
(Gly8,Aib27,β-Ala35,37,Arg38)hGLP-1(7-38)NH2; (SEQ ID NO.347)
(Gly8,Aib27,β-Ala35,37,Arg38,39)hGLP-1(7-39)NH2; (SEQ ID NO.348)
(Gly8,Lys18,27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.349)
(Gly8,Lys27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.350)
(Gly8,β-Ala35,Arg38)hGLP-1(7-38)NH2; (SEQ ID NO.351)
(Gly8,Arg26,34,β-Ala35,)hGLP-1(7-36)NH2; (SEQ ID NO.352)
(Gly8,D-Arg35)hGLP-1(7-36)NH2; (SEQ ID NO.353)
(Gly8,β-Ala35,Arg37)hGLP-1(7-37)NH2; (SEQ ID NO.354)
(Gly8,Phe31,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.355)
(Gly8,Aib35,Phe31)hGLP-1(7-36)NH2; (SEQ ID NO.356)
(Gly8,Aib35,2-Nal31)hGLP-1(7-36)NH2; (SEQ ID NO.357)
(Gly8,Aib35,2-Nal28,31)hGLP-1(7-36)NH2; (SEQ ID NO.358)
(Gly8,Aib35,Arg26,34,2-Nal31)hGLP-1(7-36)NH2; (SEQ ID NO.359)
(Gly8,Aib35,Arg26,34,Phe31)hGLP-1(7-36)NH2; (SEQ ID NO.360)
(Gly8,Aib35,2-Nal19,31)hGLP-1(7-36)NH2; (SEQ ID NO.361)
(Gly8,Aib35,2-Nal12,31)hGLP-1(7-36)NH2; (SEQ ID NO.362)
(Gly8,Aib35,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.99)
(Gly8,Aib35,Arg34,Lys26(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.364)
(Gly8,Aib35,Arg26,34,Lys36(Nε-十二烷基))hGLP-1(7-36)NH2; (SEQ ID NO.365)
(Gly8,β-Ala35,Ser37(O-癸酰基))hGLP1(7-37)-NH2; (SEQ ID NO.384)
(Gly8,Aib27,β-Ala35,37,Arg38,Lys39(Nε-辛酰基))hGLP-1(7-39)NH2;(SEQ ID NO.367)
(Gly8,Arg26,34,β-Ala35,Lys37(Nε-辛酰基))hGLP-1(7-37)NH2; (SEQ ID NO.368)
(Gly8,Arg26,34,β-Ala35,Lys37(Nε-癸酰基))hGLP-1(7-37)NH2; (SEQ ID NO.369)
或(Gly8,Arg26,34,β-Ala35,Lys37(Nε-十四烷基))hGLP-1(7-37)NH2; (SEQ ID NO.370)
14.根据权利要求12所述的化合物或其药学上可接受的盐,其中,所述化合物是:
(Ser8,Aib35,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.392)
(Ser8,Aib35,Glu23)hGLP-1(7-36)NH2; (SEQ ID NO.394)
(Ser8,Aib24,35)hGLP-1(7-36)NH2; (SEQ ID NO.395)
(Ser8,Aib35,Glu23,A6c32)hGLP-1(7-36)NH2; (SEQ ID NO.412)
(Ser8,Glu23,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.418)
(Ser8,Aib35,Arg26,34)hGLP-1(7-36)NH2; (SEQ ID NO.443)
(Ser8,Aib35,Arg26,34,Lys36(Nε-辛酰基))hGLP-1(7-36)NH2; (SEQ ID NO.501)
(Ser8,Aib35,Arg26,34,Lys36(Nε-癸酰基))hGLP-1(7-36)OH; (SEQ ID NO.716)
(Ser8,Aib35,Lys25,Arg26,34,Lys36(Nε-癸酰基))hGLP-1(7-36)OH; (SEQ ID NO.717)
(Ser8,Arg26,34,β-Ala35,Lys36(Nε-Aec-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.757)
(Ser8,Aib35,Arg26,34,Ava37,Ado38)hGLP-1(7-38)NH2; (SEQ ID NO.718)
(Ser8,Aib35,Arg26,34,Asp37,Ava38,Ado39)hGLP-1(7-39)NH2; (SEQ ID NO.719)
(Ser8,Aib35,Arg26,34,Aun37)hGLP-1(7-37)NH2; (SEQ ID NO.720)
(Ser8,Aib17,35)hGLP-1(7-36)NH2; (SEQ ID NO.389)
(Ser8,Arg26,34,β-Ala35,D-Asp37,Ava38,Aun39)hGLP-1(7-39)NH2;(SEQ ID NO.722)
(Ser8,Glu22,23,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.723)
(Ser8,Lys18,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.724)
(Ser8,Leu27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.725)
(Ser8,Lys33,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.726)
(Ser8,Lys18,Leu27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.727)
(Ser8,D-Arg36)hGLP-1(7-36)NH2; (SEQ ID NO.728)
(Ser8,β-Ala35,D-Arg37)hGLP-1(7-37)NH2; (SEQ ID NO.729)
(Ser8,Aib27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.730)
(Ser8,Aib27,β-Ala35,37,Arg38)hGLP-1(7-38)NH2; (SEQ ID NO.731)
(Ser8,Aib27,β-Ala35,37,Arg38,39)hGLP-1(7-39)NH2; (SEQ ID NO.732)
(Ser8,Lys18,27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.733)
(Ser8,Lys27,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.734)
(Ser8,β-Ala35,Arg38)hGLP-1(7-38)NH2; (SEQ ID NO.735)
(Ser8,Arg26,34,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.736)
(Ser8,D-Arg35)hGLP-1(7-36)NH2; (SEQ ID NO.737)
(Ser8,β-Ala35,Arg37)hGLP-1(7-37)NH2; (SEQ ID NO.738)
(Ser8,Phe31,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.739)
(Ser8,Aib35,Phe31)hGLP-1(7-36)NH2; (SEQ ID NO.740)
(Ser8,Aib35,2-Nal31)hGLP-1(7-36)NH2; (SEQ ID NO.741)
(Ser8,Aib35,2-Nal28,31)hGLP-1(7-36)NH2; (SEQ ID NO.742)
(Ser8,Aib35,Arg26,34,2-Nal31)hGLP-1(7-36)NH2; (SEQ ID NO.743)
(Ser8,Aib35,Arg26,34,Phe31)hGLP-1(7-36)NH2; (SEQ ID NO.744)
(Ser8,Aib35,2-Nal19,31)hGLP-1(7-36)NH2; (SEQ ID NO.745)
(Ser8,Aib35,2-Nal12,31)hGLP-1(7-36)NH2; (SEQ ID NO.746)
(Ser8,Aib35,Lys36(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.483)
(Ser8,Aib35,Arg34,Lys26(Nε-癸酰基))hGLP-1(7-36)NH2; (SEQ ID NO.748)
(Ser8,Aib35,Arg26,34,Lys36(Nε-十二烷基))hGLP-1(7-36)NH2; (SEQ ID NO.749)
(Ser8,β-Ala35,Ser37(O-十二烷基))hGLP1(7-37)-NH2; (SEQ ID NO.539)
(Ser8,Aib27,β-Ala35,37,Arg38,Lys39(Nε-辛酰基))hGLP-1(7-39)NH2; (SEQ ID NO.751)
(Ser8,Arg26,34,β-Ala35,Lys37(Nε-辛酰基))hGLP-1(7-37)NH2; (SEQ ID NO.752)
(Ser8,Arg26,34,β-Ala35,Lys37(Nε-癸酰基))hGLP-1(7-37)NH2; (SEQ ID NO.753)
或(Ser8,Arg26,34,β-Ala35,Lys37(Nε-十四烷酰基))hGLP-1(7-37)NH2; (SEQ ID NO.754)
15.根据权利要求1所述的化合物或其药学上可接受的盐,其中,所述化合物是:
(Ser8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.767)
(Abu8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.768)
(Val8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.769)
(β-Ala8,35)hGLP-1(7-36)NH2; (SEQ ID NO.770)
(Abu8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.771)
(Val8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.772)
或(β-Ala8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.773)。
16.根据权利要求15所述的化合物或其药学上可接受的盐,其中,所述化合物是:
(Ser8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.767)
(Abu8,β-Ala35)hGLP-1(7-36)NH2; (SEQ ID NO.768)
或(Abu8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.771)。
17.根据权利要求16所述的化合物或其药学上可接受的盐,其中,所述化合物是:
(Ser8,Aib35)hGLP-1(7-36)NH2; (SEQ ID NO.767)。
18.一种药物组合物,包括有效量的权利要求1所述的化合物或其药学上可接受的盐,以及药学上可接受的载体或稀释剂。
19.一种使患者的GLP-1受体引起激动剂作用的方法,所述方法包括以有效量的权利要求1所述的化合物或其药学上可接受的盐向所述的患者给药。
20.一种治疗患者所患有的选自以下疾病的方法:I型糖尿病、II型糖尿病、肥胖症、胰高血糖素瘤、气管分泌性疾病、代谢性疾病、关节炎、骨质疏松症、中枢神经系统疾病、再狭窄和神经变性疾病,所述的方法包括以有效量的权利要求1的化合物或其药学上可接受的盐向所述患者给药。
21.根据权利要求20所述的方法,其中,所述的疾病是I型糖尿病或II型糖尿病。
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JP2007524579A (ja) | 2003-02-19 | 2007-08-30 | ソシエテ・ドゥ・コンセイユ・ドゥ・ルシェルシュ・エ・ダプリカーション・シャンティフィック・エス・ア・エス | Glp−1の類似体 |
TW200522976A (en) | 2003-09-19 | 2005-07-16 | Novo Nordisk As | Novel plasma protein affinity tags |
EP1711523B1 (en) * | 2003-12-16 | 2012-10-10 | Ipsen Pharma | Analogues of glp-1 |
BRPI0608516A2 (pt) | 2005-03-18 | 2010-11-16 | Novo Nordisk As | análogo de glp-1, método para aumentar o tempo de ação em um paciente de um análogo de glp-1, composição farmacêutica, e, uso de um composto |
TWI362392B (en) | 2005-03-18 | 2012-04-21 | Novo Nordisk As | Acylated glp-1 compounds |
ES2390286T3 (es) | 2005-12-16 | 2012-11-08 | Nektar Therapeutics | Conjugados poliméricos de GLP-1 |
CA2648936C (en) | 2006-04-20 | 2013-07-09 | Amgen Inc. | Glp-1 compounds |
GB2448895A (en) * | 2007-05-01 | 2008-11-05 | Activotec Spp Ltd | GLP-1 like compounds and uses thereof |
SG192405A1 (en) * | 2008-06-17 | 2013-08-30 | Univ Indiana Res & Tech Corp | Gip-based mixed agonists for treatment of metabolic disorders and obesity |
RU2526804C2 (ru) | 2008-08-06 | 2014-08-27 | Ново Нордиск Хелс Кеа Аг | Конъюгированные белки с пролонгированным действием in vivo |
US8513192B2 (en) | 2009-01-22 | 2013-08-20 | Novo Nordisk A/S | Stable growth hormone compounds resistant to proteolytic degradation |
SG175411A1 (en) * | 2009-05-01 | 2011-12-29 | Hoffmann La Roche | Insulinotropic peptide synthesis using solid and solution phase combination techniques |
CN105963710A (zh) | 2009-08-06 | 2016-09-28 | 诺沃—诺迪斯克保健股份有限公司 | 具有延长的体内功效的生长激素 |
BR112012018116B1 (pt) | 2010-01-22 | 2022-06-21 | Novo Nordisk Health Care Ag | Conjugados de hormônio do crescimento com eficácia in vivo prolongada |
JP5980689B2 (ja) | 2010-01-22 | 2016-08-31 | ノヴォ・ノルディスク・ヘルス・ケア・アーゲー | 安定な成長ホルモン化合物 |
WO2012054861A1 (en) | 2010-10-22 | 2012-04-26 | Nektar Therapeutics | Glp-1 polymer conjugates having a releasable linkage |
WO2012054822A1 (en) | 2010-10-22 | 2012-04-26 | Nektar Therapeutics | Pharmacologically active polymer-glp-1 conjugates |
TWI588153B (zh) | 2012-05-18 | 2017-06-21 | 中國醫藥大學 | 多胜肽、編碼該多胜肽之核酸分子、以及該多胜肽之應用 |
EP2981282B1 (en) | 2013-04-05 | 2020-11-04 | Novo Nordisk Health Care AG | Growth hormone compound formulation |
PL3393496T3 (pl) | 2015-12-23 | 2024-04-22 | The Johns Hopkins University | Długo działający agonista glp-1r jako terapia stanów neurologicznych i neurodegeneracyjnych |
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US1539498A (en) | 1925-05-26 | And fifteen | ||
US5545618A (en) * | 1990-01-24 | 1996-08-13 | Buckley; Douglas I. | GLP-1 analogs useful for diabetes treatment |
US5672659A (en) | 1993-01-06 | 1997-09-30 | Kinerton Limited | Ionic molecular conjugates of biodegradable polyesters and bioactive polypeptides |
US5705483A (en) * | 1993-12-09 | 1998-01-06 | Eli Lilly And Company | Glucagon-like insulinotropic peptides, compositions and methods |
US5595760A (en) | 1994-09-02 | 1997-01-21 | Delab | Sustained release of peptides from pharmaceutical compositions |
US5512549A (en) * | 1994-10-18 | 1996-04-30 | Eli Lilly And Company | Glucagon-like insulinotropic peptide analogs, compositions, and methods of use |
US6268343B1 (en) * | 1996-08-30 | 2001-07-31 | Novo Nordisk A/S | Derivatives of GLP-1 analogs |
US6458924B2 (en) * | 1996-08-30 | 2002-10-01 | Novo Nordisk A/S | Derivatives of GLP-1 analogs |
AU2610699A (en) * | 1998-02-27 | 1999-09-15 | Novo Nordisk A/S | Derivatives of glp-1 analogs |
FR2777283B1 (fr) * | 1998-04-10 | 2000-11-24 | Adir | Nouveaux composes peptidiques analogues du glucagon-peptide- 1 (7-37), leur procede de preparation et les compositions pharmaceutiques qui les contiennent |
US6720407B1 (en) * | 1998-08-28 | 2004-04-13 | Eli Lilly And Company | Method for administering insulinotropic peptides |
KR20050037004A (ko) * | 1998-12-07 | 2005-04-20 | 소시에떼 더 콘세이유 더 레세르세 에 다플리까띠옹 시엔띠피끄, 에스.아.에스. | Glp-1의 유사체 |
WO2000034332A1 (en) * | 1998-12-07 | 2000-06-15 | Societe De Conseils De Recherches Et D'applications Scientifiques Sas | Glp-1 analogues |
EP1239871A1 (en) * | 1999-11-12 | 2002-09-18 | Novo Nordisk A/S | Use of glp-1 agonists for the inhibition of beta cell degeneration |
US6844321B2 (en) * | 2000-01-31 | 2005-01-18 | Novo Nordisk A/S | Crystallization of a GLP-1 analogue |
AU2001264791B2 (en) * | 2000-06-16 | 2006-11-23 | Eli Lilly And Company | Glucagon-like peptide-1 analogs |
JP2007524579A (ja) | 2003-02-19 | 2007-08-30 | ソシエテ・ドゥ・コンセイユ・ドゥ・ルシェルシュ・エ・ダプリカーション・シャンティフィック・エス・ア・エス | Glp−1の類似体 |
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- 2004-02-17 DE DE602004025205T patent/DE602004025205D1/de not_active Expired - Lifetime
- 2004-02-17 ES ES04711811T patent/ES2336563T3/es not_active Expired - Lifetime
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WO2004074315A3 (en) | 2004-11-25 |
WO2004074315A2 (en) | 2004-09-02 |
EP1594529A2 (en) | 2005-11-16 |
EP1594529A4 (en) | 2008-01-16 |
ATE455555T1 (de) | 2010-02-15 |
US20060217300A1 (en) | 2006-09-28 |
TWI283684B (en) | 2007-07-11 |
EP1594529B1 (en) | 2010-01-20 |
EP2067483A1 (en) | 2009-06-10 |
AR043365A1 (es) | 2005-07-27 |
CN101942018A (zh) | 2011-01-12 |
CA2513307A1 (en) | 2004-09-02 |
HK1083762A1 (en) | 2006-07-14 |
JP2007524579A (ja) | 2007-08-30 |
TW200418877A (en) | 2004-10-01 |
ES2336563T3 (es) | 2010-04-14 |
DE602004025205D1 (de) | 2010-03-11 |
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