RU2001118839A - ANALOGUES GPP-1 - Google Patents

ANALOGUES GPP-1

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RU2001118839A
RU2001118839A RU2001118839/04A RU2001118839A RU2001118839A RU 2001118839 A RU2001118839 A RU 2001118839A RU 2001118839/04 A RU2001118839/04 A RU 2001118839/04A RU 2001118839 A RU2001118839 A RU 2001118839A RU 2001118839 A RU2001118839 A RU 2001118839A
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ala
hgpp
seq
pal
aib
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RU2001118839/04A
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RU2208015C2 (en
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Женг Ксин Донг
Дэвид Х. КОЙ
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Сосьете Де Консей Де Решерш Э Д`Аппликасьон Сьентифик Сас
Дзе Администрейторс Оф Дзе Тьюлейн Эдьюкейшнл Фанд
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Claims (12)

1. Соединение формулы (I)1. The compound of formula (I) (R2R3)-А7-А8-А9-А10-А11-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-R1, (I)(R 2 R 3 ) -A 7 -A 8 -A 9 -A 10 -A 11 -A 12 -A 13 -A 14 -A 15 -A 16 -A 17 -A 18 -A 19 -A 20 -A 21 -A 22 -A 23- A 24 -A 25 -A 26 -A 27 -A 28 -A 29 -A 30 -A 31 -A 32 -A 33 -A 34 -A 35 -A 36 -A 37 - R 1 , (I) где А7 представляет собой L-His, Ura, Paa, Pta, D-His, Tyr, 3-Pal, 4-Pal, Hppa, Tma-His, Amp или делетирована, при условии, что если А7 представляет собой Ura, Paa, Pta или Hppa, то R2 и R3 делегированы;where A 7 represents L-His, Ura, Paa, Pta, D-His, Tyr, 3-Pal, 4-Pal, Hppa, Tma-His, Amp or is deleted, provided that if A 7 represents Ura, Paa, Pta or Hppa, then R 2 and R 3 are delegated; А8 означает Ala, D-Ala, Aib, Acc, N-Me-Ala, N-Me-D-Ala, Arg или N-Me-Gly;A 8 is Ala, D-Ala, Aib, Acc, N-Me-Ala, N-Me-D-Ala, Arg or N-Me-Gly; А9 означает Glu, N-Me-Glu, N-Me-Asp или Asp;And 9 means Glu, N-Me-Glu, N-Me-Asp or Asp; А10 означает Gly, Acc, Ala, D-Ala, Phe или Aib;And 10 means Gly, Acc, Ala, D-Ala, Phe or Aib; A11 означает Thr или Ser;A 11 means Thr or Ser; А12 означает Phe, Acc, Aic, Aib, 3-Pal, 4-Pal, β-Nal, Cha, Trp или Xl-Phe;And 12 is Phe, Acc, Aic, Aib, 3-Pal, 4-Pal, β-Nal, Cha, Trp or X 1 -Phe; А13 означает Thr или Ser;A 13 means Thr or Ser; А14 означает Ser, Thr, Ala или Aib;A 14 is Ser, Thr, Ala or Aib; А15 означает Asp, Ala, D-Asp или Glu;A 15 is Asp, Ala, D-Asp or Glu; А16 означает Val, D-Val, Acc, Aib, Leu, Ile. Tle, Nle, Abu, Ala, D-Ala, Tba или Cha;And 16 means Val, D-Val, Acc, Aib, Leu, Ile. Tle, Nle, Abu, Ala, D-Ala, Tba or Cha; А17 означает Ser, Ala, D-Ala, Aib, Acc или Thr;A 17 is Ser, Ala, D-Ala, Aib, Acc or Thr; А18 означает Ser, Ala, D-Ala, Aib, Acc или Thr;A 18 is Ser, Ala, D-Ala, Aib, Acc or Thr; А19 означает Tyr, D-Tyr, Cha, Phe, 3-Pal, 4-Pal, Acc, β-Nal, Amp или X1-Phe;And 19 means Tyr, D-Tyr, Cha, Phe, 3-Pal, 4-Pal, Acc, β-Nal, Amp or X 1 -Phe; А20 означает Leu, Ala, Acc, Aib, Nle, Ile, Cha, Tle, Val, Phe или X1-Phe;And 20 means Leu, Ala, Acc, Aib, Nle, Ile, Cha, Tle, Val, Phe or X 1 -Phe; А21 означает Glu, Ala или Asp;A 21 means Glu, Ala or Asp; А22 означает Gly, Acc, Ala, D-Ala, β-Ala или Aib;A 22 means Gly, Acc, Ala, D-Ala, β-Ala or Aib; А23 означает Gln, Asp, Ala, D-Ala, Aib, Acc, Asn или Glu;A 23 means Gln, Asp, Ala, D-Ala, Aib, Acc, Asn or Glu; А24 означает Ala, Aib, Val, Abu, Tle или Acc;A 24 means Ala, Aib, Val, Abu, Tle or Acc; А25 означает Ala, Aib, Val, Abu, Tle, Acc, Lys, Arg, hArg, Orn, HN-CH((CH2)n-NR10R11)-С(О) или HN-CH((CH2)e-X3)-С(О);A 25 means Ala, Aib, Val, Abu, Tle, Acc, Lys, Arg, hArg, Orn, HN-CH ((CH 2 ) n -NR 10 R 11 ) -C (O) or HN-CH ((CH 2 ) e —X 3 ) —C (O); А26 означает Lys, Ala, 3-Pal, 4-Pal, Arg, hArg, Orn, Amp, HN-CH((CH2)n-NR10R11-C(O) или HN-CH((СН2)е-Х3)-С(О);A 26 means Lys, Ala, 3-Pal, 4-Pal, Arg, hArg, Orn, Amp, HN-CH ((CH 2 ) n -NR 10 R 11 -C (O) or HN-CH ((CH 2 ) e -X 3 ) -C (O); А27 означает Glu, Ala, D-Ala или Asp;A 27 means Glu, Ala, D-Ala or Asp; А28 означает Phe, Ala, Pal, β-Nal, Xl-Phe, Aic, Acc, Aib, Cha или Trp;A 28 means Phe, Ala, Pal, β-Nal, X 1 -Phe, Aic, Acc, Aib, Cha or Trp; А29 означает Ile. Acc, Aib, Leu, Nle, Cha, Tle, Val, Abu, Ala, Tba или Phe;A 29 means Ile. Acc, Aib, Leu, Nle, Cha, Tle, Val, Abu, Ala, Tba or Phe; А30 означает Ala, Aib, Acc или делетирована;And 30 means Ala, Aib, Acc or deleted; А31 означает Trp, Ala, β-Nal, 3-Pal, 4-Pal, Phe, Acc, Aib, Cha, Amp или делетирована;A 31 means Trp, Ala, β-Nal, 3-Pal, 4-Pal, Phe, Acc, Aib, Cha, Amp or is deleted; А32 означает Leu, Ala, Acc, Aib, Nle, Ile, Cha, Tle, Phe, Xl-Phe, Ala или делетирована;A 32 means Leu, Ala, Acc, Aib, Nle, Ile, Cha, Tle, Phe, X 1 -Phe, Ala or is deleted; А33 означает Val, Acc, Aib, Leu, Ile. Tle, Nle, Cha, Ala, Phe, Abu, Xl-Phe, Tba, Gaba или делетирована;And 33 means Val, Acc, Aib, Leu, Ile. Tle, Nle, Cha, Ala, Phe, Abu, X l -Phe, Tba, Gaba or deleted; А34 означает Lys, Arg, hArg, Orn, Amp, Gaba, HN-CH((CH2)n-NR10R11)-C(O), HN-CH((СН2)е-X3)-С(O) или делетирована;A 34 means Lys, Arg, hArg, Orn, Amp, Gaba, HN-CH ((CH 2 ) n -NR 10 R 11 ) -C (O), HN-CH ((CH 2 ) e -X 3 ) - C (O) or deleted; А35 означает Gly или делетирована;A 35 means Gly or deleted; А36 означает L- или D-Arg, D- или L-Lys, D- или L-hArg, D- или L-Orn, Amp, HN-CH ((CH2)n-NR10R11)-С(О), HN-CH((CH2)e-X3)-С(О) или делетирована;A 36 is L- or D-Arg, D- or L-Lys, D- or L-hArg, D- or L-Orn, Amp, HN-CH ((CH 2 ) n -NR 10 R 11 ) -C (O), HN — CH ((CH 2 ) e —X 3 ) —C (O) or deleted; А37 означает Gly или делетирована;A 37 means Gly or deleted; X1 в каждом случае независимо выбран из группы, состоящей из (C1-С6) алкила, ОН и галогена;X 1 in each case is independently selected from the group consisting of (C 1 -C 6 ) alkyl, OH and halogen; R1 означает ОН, NH2, (C1-C12) алкоксигруппу или NH-X2-CH2-Z0, где Х2 является (C1-C12) углеводородным фрагментом и Z0 представляет собой Н, ОН, CO2H или CONH2;R 1 is OH, NH 2 , (C 1 -C 12 ) alkoxy, or NH-X 2 -CH 2 -Z 0 , where X 2 is a (C 1 -C 12 ) hydrocarbon moiety and Z 0 is H, OH, CO 2 H or CONH 2 ; X3 означаетX 3 means
Figure 00000001
Figure 00000001
 или -C(O)-NHR12, где X4 в каждом случае независимо представляет собой -С(О)-, -NH-C(O)- или -СН2-; f в каждом случае независимо является целым числом от 1 до 29;or —C (O) —NHR 12 , wherein X 4 in each case independently is —C (O) -, —NH — C (O) -, or —CH 2 -; f in each case is independently an integer from 1 to 29; каждый из радикалов R2 и R3 независимо выбран из группы, состоящей из Н, (С1-С30)алкила, (С2-С30)алкенила, фенил(C1-С30)алкила, нафтил(C1-С30)алкила, гидрокси(C1-С30)алкила, гидрокси(C2-С30)алкенила, гидроксифенил(C1-С30)алкила и гидроксинафтил(C1-С30)алкила; или один из радикалов R2 и R3 означает С(O)Х5, в котором X5 является (C1-С30)алкилом, (С2-С30)алкенилом, фенил(C1-С30)алкилом, нафтил(C1-С30)алкилом, гидрокси(C2-С30)алкилом, гидрокси(C2-С30)алкенилом, гидроксифенил(C1-С30)алкилом, гидроксинафтил(C1-С30)алкилом,each of the radicals R 2 and R 3 is independently selected from the group consisting of H, (C 1 -C 30 ) alkyl, (C 2 -C 30 ) alkenyl, phenyl (C 1 -C 30 ) alkyl, naphthyl (C 1 - C 30 ) alkyl, hydroxy (C 1 -C 30 ) alkyl, hydroxy (C 2 -C 30 ) alkenyl, hydroxyphenyl (C 1 -C 30 ) alkyl and hydroxy-naphthyl (C 1 -C 30 ) alkyl; or one of the radicals R 2 and R 3 means C (O) X 5 in which X 5 is (C 1 -C 30 ) alkyl, (C 2 -C 30 ) alkenyl, phenyl (C 1 -C 30 ) alkyl, naphthyl (C 1 -C 30) alkyl, hydroxy (C 2 -C 30) alkyl, hydroxy (C 2 -C 30) alkenyl, hydroxyphenyl (C 1 -C 30) alkyl, hydroxynaphthyl (C 1 -C 30) alkyl,
Figure 00000002
Figure 00000002
Figure 00000003
Figure 00000003
Figure 00000004
Figure 00000004
 где Y означает Н или ОН, r = 0-4 и q = 0-4;where Y is H or OH, r = 0-4 and q = 0-4; е независимо для каждого случая является целым числом от 1 до 4;e independently for each case is an integer from 1 to 4; n независимо для каждого случая является целым числом от 1 до 5;n independently for each case is an integer from 1 to 5; R10 и R11 независимо в каждом случае означают Н, (C1-С30)-алкил, (C1-С30)ацил, (C1-С30)алкилсульфонил, -С((NH)(NH2)) илиR 10 and R 11 independently in each case mean H, (C 1 -C 30 ) -alkyl, (C 1 -C 30 ) acyl, (C 1 -C 30 ) alkylsulfonyl, -C ((NH) (NH 2 ) ) or
Figure 00000005
Figure 00000005
 при условии, что когда R10 является (С1-С30)ацилом, (C1-С30)-алкилсульфонилом, -С((NH)(NH2)) илиwith the proviso that when R 10 is (C 1 -C 30 ) acyl, (C 1 -C 30 ) -alkylsulfonyl, -C ((NH) (NH 2 )) or
Figure 00000006
Figure 00000006
 R11 представляет собой Н или (C1-С30)алкил;R 11 represents H or (C 1 -C 30 ) alkyl; R12 является (C1-С30)алкилом;R 12 is (C 1 -C 30 ) alkyl; при условии, что: (i) по меньшей мере одна аминокислота соединения формулы (I) не та же самая, что и в нативной последовательности чГПП-1(7-36 или -37)NH2 (SEQ ID NO: 1,2) или чГПП-1(7-36 или -37)ОН (SEQ ID NO: 3,4);.(ii) соединение формулы (I) не является аналогом чГПП-1(7-36 или -37)NH2 (SEQ ID NO: 1,2) или чГПП-1(7-36 или -37)ОН (SEQ ID NO: 3,4), где одно положение замещено Ala; (iii) соединение формулы (I) не является [Lys26(Nεалканоил)]чГПП-1(7-36 или -37)-Е (SEQ ID NO:5-8), [Lys34 (Nεалканоил)]чГПП-1 (7-36 или -37)-E (SEQ ID NO:9-12), [Lys26,34-бис(Nε-алканоил)]чГПП-1 (7-36 или -37)-Е (SEQ ID NO: 13-16), [Arg26, Lys34(Nε-алканоил)]чГПП-1 (8-36 или -37)-E (SEQ ID NO: 17-20) или [Arg26,34, Lys36(Nε-алканоил)]чГПП-1(7-36 или -37)-E, где Е означает -ОН или -NH2 (SEQ ID NO: 21-24); (iv) соединение формулы (I) не является Z1-чГПП-1(7-36 или -37)-ОН, Z1-чГПП-1(7-36 или -37)-NH2, где Z1 выбран из группы, состоящей изprovided that: (i) at least one amino acid of the compound of formula (I) is not the same as in the native hGPP-1 (7-36 or -37) NH 2 sequence (SEQ ID NO: 1,2) or hGPP-1 (7-36 or -37) OH (SEQ ID NO: 3,4);. (ii) the compound of formula (I) is not an analogue of hGPP-1 (7-36 or -37) NH 2 (SEQ ID NO: 1,2) or hGPP-1 (7-36 or -37) OH (SEQ ID NO: 3,4), where one position is replaced by Ala; (iii) the compound of formula (I) is not [Lys 26 (Nε alkanoyl)] hGPP-1 (7-36 or -37) -E (SEQ ID NO: 5-8), [Lys 34 (Nε alkanoyl)] hGPP-1 (7-36 or -37) -E (SEQ ID NO: 9-12), [Lys 26.34 bis (Nε-alkanoyl)] hGPP-1 (7-36 or -37) -E (SEQ ID NO : 13-16), [Arg 26 , Lys 34 (Nε-alkanoyl)] hGPP-1 (8-36 or -37) -E (SEQ ID NO: 17-20) or [Arg 26.34 , Lys 36 ( Nε-alkanoyl)] hGPP-1 (7-36 or -37) -E, where E is —OH or —NH 2 (SEQ ID NO: 21-24); (iv) the compound of formula (I) is not Z 1 -hGPP-1 (7-36 or -37) -OH, Z 1 -hGPP-1 (7-36 or -37) -NH 2 , where Z 1 is selected from a group consisting of (a) [Arg26] (SEQ ID NO: 25-28), [Arg34] (SEQ ID NO: 29-32), [Arg26,34] (SEQ ID NO: 33-36), [Lys36] (SEQ ID NO: 37-40), [Arg26, Lys36] (SEQ ID NO: 41-44), [Arg34, Lys36] (SEQ ID NO: 45-46), [D-Lys36], [Arg36] (SEQ ID NO: 37-40), [D-Arg36], [Arg26,34, Lys36] (SEQ ID NO: 49-52) или [Arg26,36, Lys34] (SEQ ID NO: 25-28); (b) [Asp21] (SEQ ID NO: 53-56); (c) по меньшей мере одного из [Aib8] (SEQ ID NO: 57-60), [D-Ala8] и [Asp9] (SEQ ID NO: 61-64); и (d) [Tyr7] (SEQ ID NO: 65-68), [N-ацил-His7] (SEQ ID NO: 69-72), [N-алкил-His7] (SEQ ID NO: 73-76), [N-ацил-D-His7] или [N-алкил-D-His7];(a) [Arg 26 ] (SEQ ID NO: 25-28), [Arg 34 ] (SEQ ID NO: 29-32), [Arg 26.34 ] (SEQ ID NO: 33-36), [Lys 36 ] (SEQ ID NO: 37-40), [Arg 26 , Lys 36 ] (SEQ ID NO: 41-44), [Arg 34 , Lys 36 ] (SEQ ID NO: 45-46), [D-Lys 36 ], [Arg 36 ] (SEQ ID NO: 37-40), [D-Arg 36 ], [Arg 26.34 , Lys 36 ] (SEQ ID NO: 49-52) or [Arg 26.36 , Lys 34 ] (SEQ ID NO: 25-28); (b) [Asp 21 ] (SEQ ID NO: 53-56); (c) at least one of [Aib 8 ] (SEQ ID NO: 57-60), [D-Ala 8 ] and [Asp 9 ] (SEQ ID NO: 61-64); and (d) [Tyr 7 ] (SEQ ID NO: 65-68), [N-acyl-His 7 ] (SEQ ID NO: 69-72), [N-alkyl-His 7 ] (SEQ ID NO: 73 -76), [N-acyl-D-His 7 ] or [N-alkyl-D-His 7 ]; (v) соединение формулы (I) не является комбинацией любых из двух замещений, перечисленных в группах от (а) до (d); и (vi) соединение формулы (I) не является [N-Me-Ala8]чГПП-1(8-36 или -37) (SEQ ID NO: 77,78), [Glu15] чГПП-1(7-36 или -37) (SEQ ID NO: 79,80), [Asp21] чГПП-1(7-36 или -37) (SEQ ID NO: 53,54) или [Phe31]чГПП-1(7-36 или -37) (SEQ ID NO: 81,82).(v) the compound of formula (I) is not a combination of any of the two substitutions listed in groups (a) to (d); and (vi) the compound of formula (I) is not [N-Me-Ala 8 ] hGPP-1 (8-36 or -37) (SEQ ID NO: 77.78), [Glu 15 ] hGPP-1 (7- 36 or -37) (SEQ ID NO: 79.80), [Asp 21 ] hGPP-1 (7-36 or -37) (SEQ ID NO: 53.54) or [Phe 31 ] hGPP-1 (7- 36 or -37) (SEQ ID NO: 81.82). 2. Соединение по п.1 или его фармацевтически приемлемая соль, где А11 представляет собой Thr; А13 означает Thr; А14 означает Ser, Aib или Ala; А17 означает Ser, Ala, Aib или D-Ala; А18 означает Ser, Ala, Aib или D-Ala; А21 означает Glu или Ala; А23 означает Gin, Glu или Ala; и А27 означает Glu или Ala.2. The compound according to claim 1 or a pharmaceutically acceptable salt thereof, wherein A 11 is Thr; A 13 means Thr; A 14 is Ser, Aib or Ala; And 17 means Ser, Ala, Aib or D-Ala; A 18 is Ser, Ala, Aib or D-Ala; A 21 means Glu or Ala; A 23 means Gin, Glu or Ala; and A 27 means Glu or Ala. 3. Соединение по п.2 или его фармацевтически приемлемая соль, где А9 представляет собой Glu, N-Me-Glu или N-Me-Asp; A12 означает Phe, Acc или Aic; А16 означает Val, D-Val, Acc, Aib, Ala, Tle или D-Ala; А19 означает Tyr, 3-Pal, 4-Pal или D-Tyr; А20 означает Leu, Acc, Cha, Ala или Tle; А24 означает Ala, Aib или Acc; А25 означает Ala, Aib, Acc, Lys, Arg, hArg, Orn, HN-CH((CH2)n-NH-R10-C(O); А28 означает Phe или Ala; А29 означает Ile, Acc или Tle; А30 означает Ala, Aib или делетирована; А31 означает Trp, Ala, 3-Pal, 4-Pal или делетирована; А32 означает Leu, Acc, Cha, Ala или делетирована; А33 означает Val, Асс, Ala, Gaba, Tle или делетирована.3. The compound according to claim 2 or a pharmaceutically acceptable salt thereof, wherein A 9 is Glu, N-Me-Glu or N-Me-Asp; A 12 means Phe, Acc or Aic; A 16 means Val, D-Val, Acc, Aib, Ala, Tle or D-Ala; And 19 is Tyr, 3-Pal, 4-Pal or D-Tyr; And 20 means Leu, Acc, Cha, Ala or Tle; A 24 means Ala, Aib or Acc; A 25 means Ala, Aib, Acc, Lys, Arg, hArg, Orn, HN-CH ((CH 2 ) n -NH-R 10 -C (O); A 28 means Phe or Ala; A 29 means Ile, Acc or Tle; A 30 means Ala, Aib or deleted; A 31 means Trp, Ala, 3-Pal, 4-Pal or deleted; A 32 means Leu, Acc, Cha, Ala or deleted; A 33 means Val, Ass, Ala , Gaba, tle or deleted. 4. Соединение по п.3 или его фармацевтически приемлемая соль, где А8 представляет собой Ala, D-Ala, Aib, A6c, A5c, N-Me-Ala, N-Me-D-Ala или N-Me-Gly; А10 означает Gly, Ala, D-Ala или Phe; А12 означает Phe, A6c, или A5c; А16 означает Val, Ala, Tle, A6c, A5c или D-Val; А20 означает Leu, A6c, A5c, Cha, Ala или Tle; А22 означает Gly, Aib, β-Ala, L-Ala или D-Ala; А24 означает Ala или Aib; А29 означает Ile, А6с, А5с или Tle; А32 означает Leu, A6c, A5c, Cha, Ala или делетирована; А33 означает Val, A6c, A5c, Ala, Gaba, Tle или делетирована.4. The compound according to claim 3 or a pharmaceutically acceptable salt thereof, wherein A 8 is Ala, D-Ala, Aib, A6c, A5c, N-Me-Ala, N-Me-D-Ala or N-Me-Gly; And 10 means Gly, Ala, D-Ala or Phe; And 12 means Phe, A6c, or A5c; A 16 means Val, Ala, Tle, A6c, A5c or D-Val; And 20 means Leu, A6c, A5c, Cha, Ala or Tle; A 22 means Gly, Aib, β-Ala, L-Ala or D-Ala; A 24 means Ala or Aib; A 29 means Ile, A6c, A5c or Tle; A 32 means Leu, A6c, A5c, Cha, Ala or is deleted; A 33 means Val, A6c, A5c, Ala, Gaba, Tle or deleted. 5. Соединение по п.4 или его фармацевтически приемлемая соль, где R1 представляет собой ОН или NH2.5. The compound according to claim 4 or its pharmaceutically acceptable salt, where R 1 represents OH or NH 2 . 6. Соединение по п.5 или его фармацевтически приемлемая соль, где R2 представляет собой Н и R3 означает (C1-С30)алкил, (С2-С30)алкенил, (C1-С30)ацил,6. The compound according to claim 5 or its pharmaceutically acceptable salt, where R 2 represents H and R 3 means (C 1 -C 30 ) alkyl, (C 2 -C 30 ) alkenyl, (C 1 -C 30 ) acyl,
Figure 00000007
Figure 00000007
Figure 00000008
Figure 00000008
Figure 00000009
Figure 00000009
 7. Соединение по п.1, где указанным соединением является7. The compound according to claim 1, where the specified connection is [D-Ala8, Ala17,22,23,27, 3-Pal19,31, Gaba34]-ГПП-1(7-34)NH2;[D-Ala 8 , Ala 17,22,23,27 , 3-Pal 19,31 , Gaba 34 ] -GPP-1 (7-34) NH 2 ; [D-Ala8,23,27, 3-Pal19,31]чГПП-1(7-35)-NH2;[D-Ala 8.23.27 , 3-Pal 19.31 ] hGPP-1 (7-35) -NH 2 ; [Ala18,23,27, 3-Pal19,31]чГПП-1(7-35)-NH2; (SEQ ID NO: 83);[Ala 18.23.23 , 3-Pal 19.31 ] hGPP-1 (7-35) -NH 2 ; (SEQ ID NO: 83); [Ala16,23,27, 3-Pal19,31]чГПП-1(7-35)-NH2 (SEQ ID NO: 84);[Ala 16.23.23 , 3-Pal 19.31 ] hGPP-1 (7-35) -NH 2 (SEQ ID NO: 84); [Ala14,23,27, 3-Pal19,31]чГПП-1(7-35)-NH2 (SEQ ID NO: 85);[Ala 14.23.23 , 3-Pal 19.31 ] hGPP-1 (7-35) -NH 2 (SEQ ID NO: 85); [Ala22,23,27, 3-Pal19,31]чГПП-1(7-35)-NH2 (SEQ ID NO: 86);[Ala 22.23.23 , 3-Pal 19.31 ] hGPP-1 (7-35) -NH 2 (SEQ ID NO: 86); [Нрра7]чГПП-1(7-36)-NH2 (SEQ ID NO: 87);[Nrra 7 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 87); [Ala15,23,27, 3-Pal19,31]чГПП-1(7-35)-NH2 (SEQ ID NO: 88);[Ala 15.23.23 , 3-Pal 19.31 ] hGPP-1 (7-35) -NH 2 (SEQ ID NO: 88); [Ala17,23,27, 3-Pal19,31]чГПП-1(7-35)-NH2 (SEQ ID NO: 89);[Ala 17.23.23 , 3-Pal 19.31 ] hGPP-1 (7-35) -NH 2 (SEQ ID NO: 89); [Ala22,23,27, 3-Pal19,31, Gaba34]чГПП-1(7-34)-NH2 (SEQ ID NO: 90);[Ala 22.23.23 , 3-Pal 19.31 , Gaba 34 ] hGPP-1 (7-34) -NH 2 (SEQ ID NO: 90); [Ala15,22,23,27, 3-Pal19,31, Gaba34]чГПП-1(7-34)-NH2 SEQ ID NO: 91);[Ala 15,22,23,27 , 3-Pal 19.31 , Gaba 34 ] hGPP-1 (7-34) -NH 2 SEQ ID NO: 91); [Ala17,22,23,27, 3-Pal19,31, Gaba34]чГПП-1(7-34)-NH2 SEQ ID NO: 92);[Ala 17,22,23,27 , 3-Pal 19.31 , Gaba 34 ] hGPP-1 (7-34) -NH 2 SEQ ID NO: 92); [Ala18,22,23,27, 3-Pal19,31, Gaba34]чГПП-l(7-34)-NH2 (SEQ ID NO: 93);[Ala 18,22,23,27 , 3-Pal 19.31 , Gaba 34 ] hGPP-l (7-34) -NH 2 (SEQ ID NO: 93); [Ala21,22,23,27, 3-Pal19,31, Gaba34]чГПП-1(7-34)-NH2 (SEQ ID NO: 94);[Ala 21,22,23,27 , 3-Pal 19.31 , Gaba 34 ] hGPP-1 (7-34) -NH 2 (SEQ ID NO: 94); [Ala22,23,26,27, 3-Pal19,31, Gaba34]чГПП-1(7-34)-NH2 (SEQ ID NO: 95);[Ala 22,23,26,27 , 3-Pal 19.31 , Gaba 34 ] hGPP-1 (7-34) -NH 2 (SEQ ID NO: 95); [Ala22,23,27,32, 3-Pal19,31, Gaba34]чГПП-1(7-34)-NH2 (SEQ ID NO: 96);[Ala 22,23,27,32 , 3-Pal 19.31 , Gaba 34 ] hGPP-1 (7-34) -NH 2 (SEQ ID NO: 96); [Ala22,23,26,27, 3-Pal19,31, Gaba33]чГПП-1(7-33)-NH2 (SEQ ID NO: 97);[Ala 22,23,26,27 , 3-Pal 19.31 , Gaba 33 ] hGPP-1 (7-33) -NH 2 (SEQ ID NO: 97); [Ala22,23,27,31, 3-Pal19, Gaba33]чГПП-1(7-33)-NH2 (SEQ ID NO: 98);[Ala 22,23,27,31 , 3-Pal 19 , Gaba 33 ] hGPP-1 (7-33) -NH 2 (SEQ ID NO: 98); [Ala22,23,27,28, 3-Pal19,31, Gabaзз]чГПП-1(7-33)-NH2 (SEQ ID NO: 99);[Ala 22,23,27,28 , 3-Pal 19.31 , Gaba ss ] hGPP-1 (7-33) -NH 2 (SEQ ID NO: 99); [Ala22,23,27,29, 3-Pal19,31, Gaba]чГПП-1(7-33)-NH2 (SEQ ID NO: 100);[Ala 22,23,27,29 , 3-Pal 19.31 , Gaba] hGPP-1 (7-33) -NH 2 (SEQ ID NO: 100); [Ala23,27, 3-Pal19,31, Gabaзз]чГПП-1(7-33)-NH2 (SEQ ID NO: 101);[Ala 23.27 , 3-Pal 19.31 , Gaba ss ] hGPP-1 (7-33) -NH 2 (SEQ ID NO: 101); [Ala20,22,23,27, 3-Pal19,31, Gabaзз]чГПП-1(7-33)-NH2 (SEQ ID NO: 102);[Ala 20,22,23,27 , 3-Pal 19.31 , Gaba ss ] hGPP-1 (7-33) -NH 2 (SEQ ID NO: 102); [Ala22,23,27, 3-Pal19,31, Gaba33]чГПП-1(7-33)-NH2 (SEQ ID NO: 103);[Ala 22.23.27 , 3-Pal 19.31 , Gaba 33 ] hGPP-1 (7-33) -NH 2 (SEQ ID NO: 103); [Ala17,22,23,27, 3-Pal19,31, Gabaзз]чГПП-1(7-33)-NH2 (SEQ ID NO: 104);[Ala 17,22,23,27 , 3-Pal 19.31 , Gaba ss ] hGPP-1 (7-33) -NH 2 (SEQ ID NO: 104); [D-Ala10, Ala22,23,27, 3-Pal19,31, Gaba33]чГПП-1(7-33)-NH2;[D-Ala 10 , Ala 22,23,27 , 3-Pal 19,31 , Gaba 33 ] hGPP-1 (7-33) -NH 2 ; [D-Ala8, Ala17,23,27, 3-Pal19,31]чГПП-1(7-34)-NH2;[D-Ala 8 , Ala 17.23.23 , 3-Pal 19.31 ] hGPP-1 (7-34) -NH 2 ; [Ala17,23,27, 3-Pal19,26,31]чГПП-1(7-34)-NH2; (SEQ ID NO: 105);[Ala 17.23.23 , 3-Pal 19.26.31 ] hGPP-1 (7-34) -NH 2 ; (SEQ ID NO: 105); [D-Ala8, Ala17, 3-Pal19,31]чГПП-1(7-34)-NH2;[D-Ala 8 , Ala 17 , 3-Pal 19.31 ] hGPP-1 (7-34) -NH 2 ; [Ala17,23,27, 3-Pal19,31]чГПП-1(7-34)-NH2; (SEQ ID NO: 106);[Ala 17.23.23 , 3-Pal 19.31 ] hGPP-1 (7-34) -NH 2 ; (SEQ ID NO: 106); [D-Ala8, Ala17,23,27, 3-Pal19,31, Tle29]чГПП-1(7-34)-NH2;[D-Ala 8 , Ala 17.23.23 , 3-Pal 19.31 , Tle 29 ] hGPP-1 (7-34) -NH 2 ; [D-Ala8, Ala17,23,27, 3-Pal19,31, Tle16]чГПП-1(7-34)-NH2;[D-Ala 8 , Ala 17,23,27 , 3-Pal 19,31 , Tle 16 ] hGPP-1 (7-34) -NH 2 ; [D-Ala8, Ala17,23,27, 3-Pal19,31, Gaba34]чГПП-1(7-34)-NH2;[D-Ala 8 , Ala 17,23,27 , 3-Pal 19,31 , Gaba 34 ] hGPP-1 (7-34) -NH 2 ; [D-Ala22, Ala17,23,27, 3-Pal19,31, Gaba34]чГПП-1(7-34)-NH2;[D-Ala 22 , Ala 17.23.23 , 3-Pal 19.31 , Gaba 34 ] hGPP-1 (7-34) -NH 2 ; [Aib8, Ala17,23,27, 3-Pal19,31, Gaba34]чГПП-1(7-34)-NH2 (SEQ ID NO: 107);[Aib 8 , Ala 17,23,27 , 3-Pal 19,31 , Gaba 34 ] hGPP-1 (7-34) -NH 2 (SEQ ID NO: 107); [D-Ala8, Ala17,22,23,27, 3-Pal19,31]чГПП-1(7-33)-NH2;[D-Ala 8 , Ala 17,22,23,27 , 3-Pal 19,31 ] hGPP-1 (7-33) -NH 2 ; [Aib8, Ala17,22,23,27, 3-Pal19,31]чГПП-1(7-33)-NH2; (SEQ ID NO: 108);[Aib 8 , Ala 17,22,23,27 , 3-Pal 19,31 ] hGPP-1 (7-33) -NH 2 ; (SEQ ID NO: 108); [Ala17,18,23,27, 3-Pal19,31, Gaba34]чГПП-1(7-34)-NH2 (SEQ ID NO: 109);[Ala 17,18,23,27 , 3-Pal 19.31 , Gaba 34 ] hGPP-1 (7-34) -NH 2 (SEQ ID NO: 109); [Ala17,23,27, 3-Pal19,31, Tle33, Gaba34]чГПП-1(7-34)-NH2; (SEQ ID NO: 110);[Ala 17,23,27 , 3-Pal 19,31 , Tle 33 , Gaba 34 ] hGPP-1 (7-34) -NH 2 ; (SEQ ID NO: 110); [Tle16, Ala17,23,27, 3-Pal13,31, Gaba34]чГПП-1 (7-34)-NH2 (SEQ ID NO: 111);[Tle 16 , Ala 17.23.23 , 3-Pal 13.31 , Gaba 34 ] hGPP-1 (7-34) -NH 2 (SEQ ID NO: 111); [N-Me-D-Ala8, Ala17,22,23,27, 3-Pal19,31]чГПП-1(7-33)-NH2;[N-Me-D-Ala 8 , Ala 17,22,23,27 , 3-Pal 19,31 ] hGPP-1 (7-33) -NH 2 ; [Aib8, Ala17,18,22,23,27, 3-Pal19,31]чГПП-1(7-33)-NH2 (SEQ ID NO: 112);[Aib 8 , Ala 17,18,22,23,27 , 3-Pal 19,31 ] hGPP-1 (7-33) -NH 2 (SEQ ID NO: 112); [Ala17,18,22,23,27, 3-Pal19,31, Tle16,20, Gaba34]чГПП-1(7-34)-NH2 (SEQ ID NO: 113);[Ala 17,18,22,23,27 , 3-Pal 19.31 , Tle 16.20 , Gaba 34 ] hGPP-1 (7-34) -NH 2 (SEQ ID NO: 113); [D-Ala8, Ala17,18,22,23,27, 3-PAl19,31, Tle16, Gaba34]чГПП-1(7-34)-NH2;[D-Ala 8 , Ala 17,18,22,23,27 , 3-PAl 19.31 , Tle 16 , Gaba 34 ] hGPP-1 (7-34) -NH 2 ; [D-Ala8,22, Ala17,18,23,27, 3-Pal19,31, Gaba34]чГПП-1(7-34)-NH2;[D-Ala 8.22 , Ala 17.18.23.23 , 3-Pal 19.31 , Gaba 34 ] hGPP-1 (7-34) -NH 2 ; [D-Ala8,18, Ala17,22,23,27, 3-Pal19,31, Gaba34]чГПП-1(7-34)-NH2;[D-Ala 8.18 , Ala 17,22,23,27 , 3-Pal 19,31 , Gaba 34 ] hGPP-1 (7-34) -NH 2 ; [D-Ala8,17, Ala18,22,23,27, 3-Pal19,31, Gaba34]чГПП-1(7-34)-NH2; или[D-Ala 8.17 , Ala 18.22 , 23.23 , 3-Pal 19.31 , Gaba 34 ] hGPP-1 (7-34) -NH 2 ; or [D-Ala8, Ala17,18,22,23,27, 3-Pal19,31, Gaba34]чГПП-1(7-34)-NH2;[D-Ala 8 , Ala 17,18,22,23,27 , 3-Pal 19,31 , Gaba 34 ] hGPP-1 (7-34) -NH 2 ; или его фармацевтически приемлемая соль.or a pharmaceutically acceptable salt thereof. 8. Соединение по п.1, где указанным соединением является8. The compound according to claim 1, where the specified connection is [Aib8, А6с32]чГПП-1(7-36)NH2 (SEQ ID NO: 114);[Aib 8 , A6c 32 ] hGPP-1 (7-36) NH 2 (SEQ ID NO: 114); [А6с20,32]чГПП-1(7-36)-NH2 (SEQ ID NO: 115);[A6c 20.32 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 115); [Aib8]чГПП-1(7-36)-NH2 (SEQ ID NO: 116);[Aib 8 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 116); [(Tma-His)7]чГПП-1(7-36)-NH2 (SEQ ID NO: 117);[(Tma-His) 7 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 117); [А6с8]чГПП-1(8-36)-NH2 (SEQ ID NO: 118);[A6c 8 ] hGPP-1 (8-36) -NH 2 (SEQ ID NO: 118); [А6с8]чГПП-1(7-36)-NH2 (SEQ ID NO: 119);[A6c 8 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 119); [А6с16,20]чГПП-1(7-36)-NH2 (SEQ ID NO: 120);[A6c 16.20 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 120); [А6с29,32]чГПП-1(7-36)-NH2 (SEQ ID NO: 121);[A6c 29.32 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 121); [A6c20, Aib24]чГПП-1(7-36)-NH2 (SEQ ID NO: 122);[A6c 20 , Aib 24 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 122); [Aib24, A6c29,32]чГПП-1(7-36)-NH2 (SEQ ID NO: 123);[Aib 24 , A6c 29.32 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 123); [A6c16,29,32]чГПП-1(7-36)-NH2 (SEQ ID NO: 124);[A6c 16,29,32 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 124); [Ura7]чГПП-1(7-36)-NH2 (SEQ ID NO: 125);[Ura 7 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 125); [Раа7]чГПП-1(7-36)-NH2 (SEQ ID NO: 126);[Raa 7 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 126); [Pta7]чГПП-1(7-36)-NH2 (SEQ ID NO: 127);[Pta 7 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 127); [N-Me-Ala8]чГПП-1(7-36)-NH2 (SEQ ID NO: 128);[N-Me-Ala 8 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 128); [N-Me-Ala8]чГПП-1(8-36)-NH2 (SEQ ID NO:);[N-Me-Ala 8 ] hGPP-1 (8-36) -NH 2 (SEQ ID NO :); [N-Me-D-Ala8]чГПП-1(7-36)-NH2;[N-Me-D-Ala 8 ] hGPP-1 (7-36) -NH 2 ; [N-Me-D-Ala8]чГПП-1(8-36)-NH2;[N-Me-D-Ala 8 ] hGPP-1 (8-36) -NH 2 ; [N-Me-Gly8]чГПП-1(7-36)-NH2 (SEQ ID NO: 129);[N-Me-Gly 8 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 129); [А5с8]чГПП-1(7-36)-NH2 (SEQ ID NO: 130);[A5c 8 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 130); [N-Me-Glu9]чГПП-1(7-36)-NH2 (SEQ ID NO: 131);[N-Me-Glu 9 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 131); [A5c8, А6с20,32]чГПП-1(7-36)-NH2 (SEQ ID NO: 132);[A5c 8 , A6c 20.32 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 132); [Aib8, А6с32]чГПП-1(7-36)-NH2 (SEQ ID NO: 133);[Aib 8 , A6c 32 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 133); [Aib8,25]чГПП-1(7-36)-NH2 (SEQ ID NO: 134);[Aib 8.25 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 134); [Aib8,24]чГПП-1(7-36)-NH2 (SEQ ID NO: 135);[Aib 8.24 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 135); [Aib8,30]чГПП-1(7-36)-NH2 (SEQ ID NO: 136);[Aib 8.30 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 136); [Aib8, Cha20]чГПП-1(7-36)-NH2 (SEQ ID NO: 137);[Aib 8 , Cha 20 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 137); [Aib8, Cha32]чГПП-1(7-36)-NH2 (SEQ ID NO: 138);[Aib 8 , Cha 32 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 138); [Aib8, Glu23]чГПП-1(7-36)-NH2 (SEQ ID NO: 139);[Aib 8 , Glu 23 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 139); [Aib8, A6c20]чГПП-1(7-36)-NH2 (SEQ ID NO: 140);[Aib 8 , A6c 20 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 140); [Aib8, А6с20,32]чГПП-1(7-36)-NH2 (SEQ ID NO: 141);[Aib 8 , A6c 20.32 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 141); [Aib8,22]чГПП-1(7-36)-NH2 (SEQ ID NO: 142);[Aib 8.22 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 142); [Aib8, β-Ala22]чГПП-1(7-36)-NH2 SEQ ID NO: 143);[Aib 8 , β-Ala 22 ] hGPP-1 (7-36) -NH 2 SEQ ID NO: 143); [Aib8, Lys25]чГПП-1(7-36)-NH2 (SEQ ID NO: 144);[Aib 8 , Lys 25 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 144); [Aib8, А6с12]чГПП-1(7-36)-NH2 (SEQ ID NO: 145);[Aib 8 , A6c 12 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 145); [Aib8, А6с29]чГПП-1(7-36)-NH2(SEQ ID NO: 146);[Aib 8 , A6c 29 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 146); [Aib8, А6с33]чГПП-1(7-36)-NH2 (SEQ ID NO: 147);[Aib 8 , A6c 33 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 147); [Aib8,14]чГПП-1(7-36)-NH2 (SEQ ID NO: 148);[Aib 8.14 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 148); [Aib8,18]чГПП-1(7-36)-NH2 (SEQ ID NO: 149);[Aib 8.18 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 149); [Aib8,17]чГПП-1(7-36)-NH2 (SEQ ID NO: 150); или[Aib 8.17 ] hGPP-1 (7-36) -NH 2 (SEQ ID NO: 150); or [Aib13, D-Arg26]чГПП-1(7-36)NH2,[Aib 13 , D-Arg 26 ] hGPP-1 (7-36) NH 2 , или его фармацевтически приемлемая соль.or a pharmaceutically acceptable salt thereof. 9. Фармацевтическая композиция, содержащая эффективное количество соединения по п.1 или его фармацевтически приемлемую соль и фармацевтически приемлемый носитель или разбавитель.9. A pharmaceutical composition comprising an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof and a pharmaceutically acceptable carrier or diluent. 10. Способ, позволяющий вызывать под влиянием агониста действие со стороны рецептора ГПП-1 у субъекта, который в этом нуждается, который включает в себя введение указанному субъекту эффективного количества соединения по п.1 или его фармацевтически приемлемой соли.10. A method for causing, under the influence of an agonist, an action on the part of the GLP-1 receptor in a subject who needs it, which comprises administering to said subject an effective amount of a compound according to claim 1 or a pharmaceutically acceptable salt thereof. 11. Способ лечения заболевания, выбранного из группы, состоящей из диабета типа I, диабета типа II, ожирения, глюкагономы, секреторных расстройств дыхательных путей, метаболического нарушения, артрита, остеопороза, заболевания центральной нервной системы, рестеноза, нейродегенеративного заболевания, почечной недостаточности, застойной сердечной недостаточности, нефротического синдрома, цирроза, отека легких и гипертензии у субъекта, который в этом нуждается, который включает в себя введение указанному субъекту эффективного количества соединения по п.1 или его фармацевтически приемлемой соли.11. A method of treating a disease selected from the group consisting of type I diabetes, type II diabetes, obesity, glucagonoma, secretory disorders of the respiratory tract, metabolic disorders, arthritis, osteoporosis, central nervous system disease, restenosis, neurodegenerative disease, renal failure, congestive heart failure, nephrotic syndrome, cirrhosis, pulmonary edema and hypertension in a subject in need thereof, which includes administering to said subject an effective amount of the unity according to claim 1 or its pharmaceutically acceptable salt. 12. Способ по п.11, при котором указанным заболеванием является диабет типа I или диабет типа II.12. The method according to claim 11, wherein said disease is type I diabetes or type II diabetes.
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