RU99106518A - GLP-1 DERIVATIVES - Google Patents

GLP-1 DERIVATIVES

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RU99106518A
RU99106518A RU99106518/04A RU99106518A RU99106518A RU 99106518 A RU99106518 A RU 99106518A RU 99106518/04 A RU99106518/04 A RU 99106518/04A RU 99106518 A RU99106518 A RU 99106518A RU 99106518 A RU99106518 A RU 99106518A
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derivative
glp
lys
amino acid
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RU2214419C2 (en
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Лиселотте Бьерре КНУДСЕН
Пер Олаф ХУУСФЕЛЬТ
Пер Франклин Нильсен
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Ново Нордиск А/С
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1. Производное GLP-1 родительского пептида, имеющее только один липофильный заместитель, который необязательно присоединен через спейсер к аминокислотному остатку, который не является N-концевым или С-концевым аминокислотным остатком, где родительский пептид имеет в сумме до пятнадцати, предпочтительно до десяти аминокислотных остатков, замененный на любой α-аминокислотный остаток, который может быть кодирован с помощью генетического кода.1. A GLP-1 derivative of the parent peptide having only one lipophilic substituent, which is optionally attached via a spacer to an amino acid residue that is not an N-terminal or C-terminal amino acid residue, where the parent peptide has up to fifteen, preferably up to ten amino acid residues residues replaced by any α-amino acid residue that can be encoded with the genetic code. 2. Производное GLP-1 растительного пептида, имеющее только два липофильных заместителя, один из которых необязательно присоединен через спейсер к С-концевому аминокислотному остатку и другой присоединен необязательно через спейсер к аминокислотному остатку, который не является N-концевым или С-концевым аминокислотным остатком, где родительский пептид имеет в сумме до пятнадцати, предпочтительно до десяти аминокислотных остатков, замененных на любой α-аминокислотный остаток, который может быть кодирован с помощью генетического кода. 2. Derived GLP-1 plant peptide having only two lipophilic substituents, one of which is optionally attached via a spacer to the C-terminal amino acid residue and the other attached optionally via a spacer to an amino acid residue that is not an N-terminal or C-terminal amino acid residue where the parent peptide has up to fifteen in total, preferably up to ten amino acid residues, replaced by any α-amino acid residue that can be encoded using the genetic code. 3. Производное GLP-1 родительского пептида, имеющее только два липофильных заместителя, которые присоединены необязательно через спейсер к аминокислотным остаткам, которые не являются N-концевыми или С-концевыми аминокислотным остатком, где родительский пептид имеет в сумме до пятнадцати, предпочтительно до десяти аминокислотных остатков, замененных на любой α-аминокислотный остаток, который может быть кодирован с помощью генетического кода. 3. The GLP-1 derivative of the parent peptide, which has only two lipophilic substituents, which are optionally attached via a spacer to amino acid residues that are not N-terminal or C-terminal amino acid residue, where the parent peptide has up to fifteen, preferably up to ten amino acid residues residues replaced by any α-amino acid residue that can be encoded with the genetic code. 4. Производное GLP-1 (7-C), где С выбирают из группы, включающей 38, 39, 40, 41, 42, 43, 44 и 45, и это производное имеет только один липофильный заместитель, который присоединен необязательно через спейсер к С-концевому аминокислотному остатку. 4. Derived GLP-1 (7-C), where C is selected from the group consisting of 38, 39, 40, 41, 42, 43, 44 and 45, and this derivative has only one lipophilic substituent, which is optionally attached via a spacer to C-terminal amino acid residue. 5. Производное GLP-1 родительского пептида, где
(а) родительский пептид представляет аналог GLP-1 (A-B), где А представляет целое число от 1 до 7, и В представляет целое число от 38 до 45, где аналог имеет в сумме до пятнадцати, предпочтительно до десяти аминокислотных остатков, замененных на любой остаток α-аминокислоты, который может быть кодирован с помощью генетического кода, и
(b) производное имеет один липофильный заместитель, присоединенный необязательно через спейсер к С-концевому аминокислотному остатку, и второй необязательный липофильный заместитель, присоединенный необязательно через спейсер к одному из других остатков аминокислот.5. Derived GLP-1 parent peptide, where
(a) the parent peptide is a GLP-1 (AB) analogue, where A represents an integer from 1 to 7, and B represents an integer from 38 to 45, where the analog has up to fifteen, preferably up to ten amino acid residues, replaced by any α-amino acid residue that can be encoded with the genetic code, and
(b) the derivative has one lipophilic substituent, optionally attached via a spacer to the C-terminal amino acid residue, and a second optional lipophilic substituent, optionally attached via a spacer to one of the other amino acid residues. 6. Производное по любому из пп.1 - 5, где родительский пептид выбирают из группы, приведенной в графической части. 6. The derivative according to any one of claims 1 to 5, wherein the parent peptide is selected from the group shown in the graphic part. 7. Производное по любому из пп.1 - 5, где родительский пептид выбирают из группы, приведенной в графической части. 7. The derivative of any one of claims 1 to 5, wherein the parent peptide is selected from the group shown in the graphic part. 8. Производное GLP-1 родительского пептида, где, по крайней мере, один аминокислотный остаток родительского пептида имеет липофильный заместитель, и родительский пептид выбирают из группы, приведенной в графической части,
при условии, что, если присутствует один липофильный заместитель, и этот заместитель присоединен к N-концевому или С-концевому аминокислотному остатку родительского пептида, то этот заместитель представляет алкильную группу или группу, которая имеет ω-карбоксильную группу.8. Derived GLP-1 of the parent peptide, where at least one amino acid residue of the parent peptide has a lipophilic substituent, and the parent peptide is selected from the group shown in the graphic part,
provided that if one lipophilic substituent is present, and this substituent is attached to the N-terminal or C-terminal amino acid residue of the parent peptide, then this substituent is an alkyl group or a group that has an ω-carboxyl group. 9. Производное по любому из предшествующих пунктов, где липофильный заместитель имеет от 4 до 40 углеродных атомов, более предпочтительно от 8 до 25 углеродных атомов. 9. The derivative according to any of the preceding claims, wherein the lipophilic substituent has from 4 to 40 carbon atoms, more preferably from 8 to 25 carbon atoms. 10. Производное по любому из предшествующих пунктов, где липофильный заместитель присоединен к аминокислотному остатку таким образом, что карбоксильная группа липофильного заместителя образует амидную связь с аминогруппой аминокислотного остатка. 10. The derivative according to any one of the preceding claims, wherein the lipophilic substituent is attached to the amino acid residue in such a way that the carboxyl group of the lipophilic substituent forms an amide bond with the amino group of the amino acid residue. 11. Производное по любому из пп.1 - 9, где липофильный заместитель присоединен к аминокислотному остатку таким образом, что аминогруппа липофильного заместителя образует амидную связь с карбоксильной группой аминокислотного остатка. 11. The derivative of any one of claims 1 to 9, wherein the lipophilic substituent is attached to the amino acid residue such that the amino group of the lipophilic substituent forms an amide bond with the carboxyl group of the amino acid residue. 12. Производное по любому из предшествующих пунктов, где липофильный заместитель присоединен к родительскому пептиду через спейсер. 12. The derivative of any of the preceding claims, wherein the lipophilic substituent is attached to the parent peptide via a spacer. 13. Производное по п.12, где спейсер представляет неразветвленную алкановую α,ω-дикарбоновую кислоту, имеющую от 1 до 7 метиленовых групп, предпочтительно две метиленовые группы, которые образуют мостик между аминогруппой родительского пептида и аминогруппой липофильного заместителя. 13. The derivative of claim 12, wherein the spacer is an unbranched alkane α, ω-dicarboxylic acid having from 1 to 7 methylene groups, preferably two methylene groups, which form a bridge between the amino group of the parent peptide and the amino group of the lipophilic substituent. 14. Производное по п.12, где спейсер представляет аминокислотный остаток, исключая Cys, или дипептид, такой как Gly-Lys. 14. The derivative of claim 12, wherein the spacer is an amino acid residue, excluding Cys, or a dipeptide, such as Gly-Lys. 15. Производное по п.14, где карбоксильная группа родительского пептида образует амидную связь с аминогруппой Lys или дипептида, содержащего Lys остаток, и другая аминогруппа Lys спейсера или спейсера-дипептида, содержащего Lys остаток, образует амидную связь с карбоксильной группой липофильного заместителя. 15. The derivative of claim 14, wherein the carboxyl group of the parent peptide forms an amide bond with the amino group of Lys or a dipeptide containing a Lys residue, and another amino group of the Lys spacer or spacer-dipeptide containing a Lys residue forms an amide bond with the carboxyl group of the lipophilic substituent. 16. Производное по п.14, где аминогруппа родительского пептида образует амидную связь с карбоксильной группой аминокислотного остатка или дипептидного спейсера, и аминогруппа аминокислотного остатка или дипептидного спейсера образует амидную связь с карбоксильной группой липофильного заместителя. 16. The derivative of claim 14, wherein the amino group of the parent peptide forms an amide bond with the carboxyl group of the amino acid residue or dipeptide spacer, and the amino group of the amino acid residue or dipeptide spacer forms an amide bond with the carboxyl group of the lipophilic substituent. 17. Производное по п.14, где карбоксильная группа родительского пептида образует амидную связь с аминогруппой спейсера-аминокислотного остатка или дипептидного спейсера, и карбоксильная группа спейсера-аминокислотного остатка или дипептидного спейсера образует амидную связь с аминогруппой группой липофильного заместителя. 17. The derivative of claim 14, wherein the carboxyl group of the parent peptide forms an amide bond with the amino group of the spacer-amino acid residue or dipeptide spacer, and the carboxyl group of the spacer-amino acid residue or dipeptide spacer forms an amide bond with the amino group with a lipophilic substituent. 18. Производное по п.14, где карбоксильная группа родительского пептида образует амидную связь с аминогруппой спейсера, который является Asp или Glu, или дипептидного спейсера, содержащего Asp или Glu остаток, и карбоксильная группа спейсера образует амидную связь с аминогруппой липофильного заместителя. 18. The derivative of claim 14, wherein the carboxyl group of the parent peptide forms an amide bond with the amino group of the spacer, which is Asp or Glu, or a dipeptide spacer containing Asp or Glu residue, and the carboxyl group of the spacer forms an amide bond with the amino group of the lipophilic substituent. 19. Производное по любому из предшествующих пунктов, где липофильный заместитель включает частично или полностью гидрированный скелет циклопентанфенантрена. 19. A derivative according to any one of the preceding claims, wherein the lipophilic substituent includes a partially or fully hydrogenated cyclopentane phenanthrene skeleton. 20. Производное по любому из пп.1 - 18, где липофильный заместитель представляет прямую или разветвленную алкильную группу. 20. The derivative according to any one of claims 1 to 18, wherein the lipophilic substituent is a straight or branched alkyl group. 21. Производное по любому из пп.1 - 18, где липофильный заместитель представляет ацильную группу жирной кислоты с прямой или разветвленной цепью. 21. The derivative according to any one of claims 1 to 18, wherein the lipophilic substituent is an acyl group of a straight or branched chain fatty acid. 22. Производное по п.21, где ацильную группу выбирают из группы, включающей CH3(CH2)nCO-, где n равно от 4 до 38, предпочтительно CH3(CH2)6CO-, CH3(CH2)8CO-, CH3(CH2)10CO-, CH3(CH2)12CO-, CH3(CH2)14CO-, CH3(CH2)16CO-, CH3(CH2)18CO-, CH3(CH2)20CO- и CH3(CH2)22CO-.22. The derivative according to claim 21, wherein the acyl group is selected from the group including CH 3 (CH 2 ) n CO-, where n is from 4 to 38, preferably CH 3 (CH 2 ) 6 CO-, CH 3 (CH 2 ) 8 CO-, CH 3 (CH 2 ) 10 CO-, CH 3 (CH 2 ) 12 CO-, CH 3 (CH 2 ) 14 CO-, CH 3 (CH 2 ) 16 CO-, CH 3 (CH 2 ) 18 CO-, CH 3 (CH 2 ) 20 CO- and CH 3 (CH 2 ) 22 CO-. 23. Производное по любому из пп.1 - 18, где липофильный заместитель представляет ацильную группу алкановой α,ω-ди-карбоновой кислоты с прямой или разветвленной цепью. 23. The derivative according to any one of claims 1 to 18, wherein the lipophilic substituent represents the acyl group of an alkanoic α, ω-dicarboxylic acid with a straight or branched chain. 24. Производное по п.23, где ацильную группу выбирают из группы, включающей HOOC(CH2)mCO-, где m равно от 4 до 38, предпочтительно от 4 до 24, более предпочтительно, выбирают из группы, включающей HOOC(CH2)14CO-, HOOC(CH2)16CO-, HOOC(CH2)18CO-, HOOC(CH2)20CO- и HOOC(CH2)22CO-.24. The derivative of claim 23, wherein the acyl group is selected from the group comprising HOOC (CH 2 ) m CO-, where m is from 4 to 38, preferably from 4 to 24, more preferably, is selected from the group including HOOC (CH 2 ) 14 CO-, HOOC (CH 2 ) 16 CO-, HOOC (CH 2 ) 18 CO-, HOOC (CH 2 ) 20 CO- and HOOC (CH 2 ) 22 CO-. 25. Производное по любому из пп.1 - 18, где липофильный заместитель со спейсером представляет группу формулы
CH3(CH2)p((CH2)qCOOH)CHNH-CO(CH2)2CO-,
где p и q представляет целые числа, и p + q представляет целое число от 8 до 33, предпочтительно от 12 до 28.25. The derivative according to any one of claims 1 to 18, wherein the lipophilic substituent with the spacer represents a group of the formula
CH 3 (CH 2 ) p ((CH 2 ) q COOH) CHNH — CO (CH 2 ) 2 CO-,
where p and q are integers, and p + q is an integer from 8 to 33, preferably from 12 to 28. 26. Производное по любому из пп.1 - 18, где липофильный заместитель со спейсером представляет группу формулы
CH3(CH2)r-NHCH(COOH)(CH2)2CO-,
где r представляет целое число от 10 до 24.26. The derivative of any one of claims 1 to 18, wherein the lipophilic substituent with the spacer represents a group of the formula
CH 3 (CH 2 ) r —NHCH (COOH) (CH 2 ) 2 CO-,
where r is an integer from 10 to 24. 27. Производное по любому из пп.1 - 18, где липофильный заместитель со спейсером представляет группу формулы
CH3(CH2)sCO-NHCH((CH2)2COOH)CO-,
где s представляет целое число от 8 до 24.27. The derivative according to any one of claims 1 to 18, wherein the lipophilic substituent with the spacer represents a group of the formula
CH 3 (CH 2 ) s CO-NHCH ((CH 2 ) 2 COOH) CO-,
where s is an integer from 8 to 24. 28. Производное по любому из пп.1 - 18, где липофильный заместитель со спейсером представляет группу формулы
-NHCH(COOH)(CH2)4NH-CO(CH2)uCH3,
где u представляет целое число от 8 до 18.28. The derivative of any one of claims 1 to 18, wherein the lipophilic substituent with the spacer represents a group of the formula
—NHCH (COOH) (CH 2 ) 4 NH — CO (CH 2 ) u CH 3 ,
where u is an integer from 8 to 18. 29. Производное по любому из пп.1 - 18, где липофильный заместитель со спейсером представляет группу формулы
NHCH(COOH)(CH2)4NH-COCH((CH2)2COOH)NH-CO(CH2)wCH3,
где w представляет целое число от 10 до 16.29. The derivative of any one of claims 1 to 18, wherein the lipophilic substituent with the spacer represents a group of the formula
NHCH (COOH) (CH 2 ) 4 NH-COCH ((CH 2 ) 2 COOH) NH-CO (CH 2 ) w CH 3 ,
where w is an integer from 10 to 16. 30. Производное по любому из пп.1 - 18, где липофильный заместитель со спейсером представляет группу формулы
NHCH(COOH)(CH2)4NH-CO(CH2)2CH(COOH)NH-CO(CH2)xCH3,
где х представляет целое число от 10 до 16.30. The derivative of any one of claims 1 to 18, wherein the lipophilic substituent with the spacer represents a group of the formula
NHCH (COOH) (CH 2 ) 4 NH-CO (CH 2 ) 2 CH (COOH) NH-CO (CH 2 ) x CH 3 ,
where x is an integer from 10 to 16. 31. Производное по любому из пп.1 - 18, где липофильный заместитель со спейсером представляет группу формулы
NHCH(COOH)(CH2)4NH-CO(CH2)2CH(COOH)NH-CO(CH2)yCH3,
где y представляет целое число от 1 до 22.31. The derivative of any of paragraphs.1-18, wherein the lipophilic substituent with the spacer represents a group of the formula
NHCH (COOH) (CH 2 ) 4 NH-CO (CH 2 ) 2 CH (COOH) NH-CO (CH 2 ) y CH 3 ,
where y is an integer from 1 to 22. 32. Производное по любому из предшествующих пунктов, в котором в сумме до шести аминокислотных остатков заменено на любой остаток α-аминокислоты, который может быть кодирован с помощью генетического кода. 32. The derivative of any of the preceding paragraphs, in which a total of up to six amino acid residues is replaced by any α-amino acid residue that can be encoded using the genetic code. 33. Производное по п.1, которое представляет Lys26 ((Nε-тетрадеканоил)-GLP-1 (7-37).33. The derivative of claim 1, which is Lys 26 ((N ε -tetradecanoyl) -GLP-1 (7-37). 34. Производное по п. 1, которое представляет Lys34 ((Nε-тетрадеканоил)-GLP-1 (7-37).34. The derivative of claim 1, which is Lys 34 ((N ε -tetradecanoyl) -GLP-1 (7-37). 35. Производное по п.3, которое представляет Lys26, 34-бис ((Nε-тетрадеканоил)-GLP-1 (7-37).35. The derivative of claim 3, which is Lys 26, 34 -bis ((N ε -tetradecanoyl) -GLP-1 (7-37). 36. Производное по п.1, которое представляет Lys26 ((Nε-тетрадеканоил)-Arg34-GLP-1 (7-37).36. The derivative of claim 1, which is Lys 26 ((N ε -tetradecanoyl) -Arg 34 -GLP-1 (7-37). 37. Производное по п. 1, которое представляет Gly8Arg26, 34Lys36 ((Nε-тетрадеканоил)-GLP-1 (7-37).37. The derivative of claim 1, which is Gly 8 Arg 26, 34 Lys 36 ((N ε -tetradecanoyl) -GLP-1 (7-37). 38. Производное по п.1, которое представляет Arg26, 34Lys36 ((Nε-тетрадеканоил)-GLP-1 (7-37).38. The derivative of claim 1, which is Arg 26, 34 Lys 36 ((N ε -tetradecanoyl) -GLP-1 (7-37). 39. Производное по п.3, которое представляет Lys26, 34-бис (
Figure 00000001
-карбоксинонадеканоил))-GLP-1 (7-37).39. The derivative of claim 3, which represents Lys 26, 34 -bis (
Figure 00000001
-carboxinonadecanoyl)) - GLP-1 (7-37). 40. Производное по п.5, которое представляет Arg26, 34Lys38 (
Figure 00000002
-карбоксинонадеканоил))-GLP-1 (7-38).40. The derivative of claim 5, which is Arg 26, 34 Lys 38 (
Figure 00000002
-carboxinonadecanoyl)) - GLP-1 (7-38). 41. Производное по п.1, которое представляет Arg34Lys26 (
Figure 00000003
-карбоксинонадеканоил))-GLP-1 (7-37).41. The derivative of claim 1, which is Arg 34 Lys 26 (
Figure 00000003
-carboxinonadecanoyl)) - GLP-1 (7-37). 42. Производное по п.1, которое представляет Arg34Lys26 (
Figure 00000004
-карбоксигептадеканоил))-GLP-1 (7-37).42. The derivative of claim 1, which is Arg 34 Lys 26 (
Figure 00000004
-carboxyheptadecanoyl)) - GLP-1 (7-37). 43. Производное по п.1, которое представляет Arg26, 34Lys36 (
Figure 00000005
-карбоксигептадеканоил))-GLP-1 (7-37).43. The derivative of claim 1, which is Arg 26, 34 Lys 36 (
Figure 00000005
-carboxyheptadecanoyl)) - GLP-1 (7-37). 44. Производное по п.5, которое представляет Arg26, 34Lys38 (
Figure 00000006
-карбоксигептадеканоил))-GLP-1 (7-38).44. The derivative of claim 5, which is Arg 26, 34 Lys 38 (
Figure 00000006
-carboxyheptadecanoyl)) - GLP-1 (7-38). 45. Производное по п.1, которое представляет Arg26, 34Lys36 (
Figure 00000007
-карбоксиундеканоил))-GLP-1 (7-37).45. The derivative of claim 1, which is Arg 26, 34 Lys 36 (
Figure 00000007
-carboxyundecanoyl)) - GLP-1 (7-37). 46. Производное по п.5, которое представляет Arg26, 34Lys38 (
Figure 00000008
-карбоксиундеканоил))-GLP-1 (7-38).46. The derivative of claim 5, which is Arg 26, 34 Lys 38 (
Figure 00000008
-carboxyundecanoyl)) - GLP-1 (7-38). 47. Производное по п.3, которое представляет Arg26, 34-бис (
Figure 00000009
-карбоксиундеканоил))-GLP-1 (7-37).47. The derivative of claim 3, which is Arg 26, 34 -bis (
Figure 00000009
-carboxyundecanoyl)) - GLP-1 (7-37). 48. Производное по п.1, которое представляет Arg34Lys26 (
Figure 00000010
-карбоксиундеканоил))-GLP-1 (7-37).48. The derivative of claim 1, which is Arg 34 Lys 26 (
Figure 00000010
-carboxyundecanoyl)) - GLP-1 (7-37). 49. Производное по п.1, которое представляет Arg34Lys26 (
Figure 00000011
-карбоксигептаноил))-GLP-1 (7-37).49. The derivative of claim 1, which is Arg 34 Lys 26 (
Figure 00000011
-carboxyheptanoyl)) - GLP-1 (7-37). 50. Производное по п.5, которое представляет Arg26,34Lys38 (
Figure 00000012
-карбоксигептаноил))-GLP-1 (7-38).50. The derivative of claim 5, which is Arg 26.34 Lys 38 (
Figure 00000012
-carboxyheptanoyl)) - GLP-1 (7-38). 51. Производное по п.1, которое представляет Arg26,34Lys36 (
Figure 00000013
карбоксигептаноил))-GLP-1 (7-37).51. The derivative of claim 1, which is Arg 26.34 Lys 36 (
Figure 00000013
carboxyheptanoyl)) - GLP-1 (7-37). 52. Производное по п.3, которое представляет Arg26,34-бис (
Figure 00000014
карбоксигептаноил))-GLP-1 (7-37).52. The derivative of claim 3, which represents Arg 26,34 -bis (
Figure 00000014
carboxyheptanoyl)) - GLP-1 (7-37). 53. Производное по п.1, которое представляет Arg34Lys26 (
Figure 00000015
карбоксипептадеканоил))-GLP-1 (7-37).53. The derivative of claim 1, which is Arg 34 Lys 26 (
Figure 00000015
carboxypeptadecanoyl)) - GLP-1 (7-37). 54. Производное по п. 1, которое представляет Arg34Lys26 ((Nε-литохолил)-GLP-1 (7-37).54. The derivative of claim 1, which is Arg 34 Lys 26 ((N ε- litocholyl) -GLP-1 (7-37). 55. Производное по п.5, которое представляет Glu22,23, 30Arg26,34Lys38 ((Nε-(γ-глутамил ((Nα-тетрадеканоил)))-GLP-1 (7-38).55. The derivative of claim 5, which is Glu 22.23, 30 Arg 26.34 Lys 38 ((N ε - (γ-glutamyl ((N α -tetradecanoyl))) - GLP-1 (7-38). 56. Производное по п. 5, которое представляет Glu23,26Arg34Lys38 ((Nε-(γ-глутамил ((Nα-тетрадеканоил)))-GLP-1 (7-38).56. The derivative of claim 5, which is Glu 23.26 Arg 34 Lys 38 ((N ε - (γ-glutamyl ((N α -tetradecanoyl))) - GLP-1 (7-38). 57. Производное по п.3, которое представляет Lys26,34-бис (
Figure 00000016
карбокситридеканоил))-GLP-1 (7-37).57. The derivative of claim 3, which represents Lys 26,34 -bis (
Figure 00000016
carboxytridecanoyl)) - GLP-1 (7-37). 58. Производное по п.3, которое представляет Lys26,34-бис (
Figure 00000017
глутамил ((Nα-тетрадеканоил)))-GLP-1 (7-37).58. The derivative of claim 3, which represents Lys 26,34 -bis (
Figure 00000017
glutamyl ((N α -tetradecanoyl))) - GLP-1 (7-37). 59. Производное по п.5, которое представляет Arg26,34Lys38 (
Figure 00000018
карбоксипептадеканоил))-GLP-1 (7-38).59. The derivative of claim 5, which is Arg 26.34 Lys 38 (
Figure 00000018
carboxypeptadecanoyl)) - GLP-1 (7-38). 60. Производное по п.3, которое представляет Lys26,34-бис (
Figure 00000019
глутамил ((Nα-гексадеканоил)))-GLP-1 (7-37).60. The derivative of claim 3, which represents Lys 26,34 -bis (
Figure 00000019
glutamyl ((N α -hexadecanoyl))) - GLP-1 (7-37). 61. Производное по п.1, которое представляет Arg34Lys26 (
Figure 00000020
глутамил ((Nα-гексадеканоил)))-GLP-1 (7-37).61. The derivative of claim 1, which is Arg 34 Lys 26 (
Figure 00000020
glutamyl ((N α -hexadecanoyl))) - GLP-1 (7-37). 62. Производное по п.5, которое представляет Arg26,34Lys38 (
Figure 00000021
глутамил ((Nα-тетрадеканоил)))-GLP-1 (7-38).62. The derivative of claim 5, which is Arg 26.34 Lys 38 (
Figure 00000021
glutamyl ((N α -tetradecanoyl))) - GLP-1 (7-38). 63. Производное по п.5, которое представляет Arg26,34Lys38 (
Figure 00000022
карбоксипептадеканоил))-GLP-1 (7-38).63. The derivative of claim 5, which is Arg 26.34 Lys 38 (
Figure 00000022
carboxypeptadecanoyl)) - GLP-1 (7-38). 64. Производное по п.5, которое представляет Arg26,34Lys36 (
Figure 00000023
глутамил ((Nα-гексадеканоил)))-GLP-1 (7-38).64. The derivative of claim 5, which is Arg 26.34 Lys 36 (
Figure 00000023
glutamyl ((N α -hexadecanoyl))) - GLP-1 (7-38). 65. Производное по п. 5, которое представляет Arg18,23, 26, 30,34Lys38 ((Nε-гексадеканоил))-GLP-1 (7-38).65. The derivative of claim 5, which is Arg 18.23, 26, 30.34 Lys 38 ((N ε -hexadecanoyl)) - GLP-1 (7-38). 66. Производное по п.5, которое представляет Arg26,34Lys38 (
Figure 00000024
карбокситридеканоил))-GLP-1 (7-38).66. The derivative of claim 5, which is Arg 26.34 Lys 38 (
Figure 00000024
carboxytridecanoyl)) - GLP-1 (7-38). 67. Производное по п.1, которое представляет Arg34Lys26 (
Figure 00000025
глутамил ((Nα-тетрадеканоил)))-GLP-1 (7-37).67. The derivative of claim 1, which is Arg 34 Lys 26 (
Figure 00000025
glutamyl ((N α -tetradecanoyl))) - GLP-1 (7-37). 68. Производное по п.5, которое представляет Arg26,34Lys38 (
Figure 00000026
глутамил ((Nα-октадеканоил)))-GLP-1 (7-38).68. The derivative of claim 5, which is Arg 26.34 Lys 38 (
Figure 00000026
glutamyl ((N α -octadecanoyl))) - GLP-1 (7-38). 69. Фармацевтическая композиция, включающая производное по любому из пп. 1 - 68 и фармацевтически приемлемый разбавитель или носитель. 69. Pharmaceutical composition comprising a derivative according to any one of paragraphs. 1 to 68 and a pharmaceutically acceptable diluent or carrier. 70. Производное по любому из пп.1 - 68 для получения лекарственного средства, которое имеет пролонгированный профиль действия по сравнению с GLP-1 (7-37). 70. The derivative of any one of claims 1 to 68 for the manufacture of a medicament that has a prolonged action profile as compared to GLP-1 (7-37). 71. Производное по любому из пп.1 - 68 для получения лекарственного средства для лечения инсулин-независимого сахарного диабета. 71. The derivative of any of paragraphs 1 to 68 for the preparation of a medicament for the treatment of insulin-independent diabetes mellitus. 72. Производное по любому из пп.1 - 68 для получения лекарственного средства для лечения инсулин-зависимого сахарного диабета. 72. The derivative of any one of claims 1 to 68 for the preparation of a medicament for the treatment of insulin-dependent diabetes mellitus. 73. Производное по любому из пп.1 - 68 для получения лекарственного средства для лечения ожирения. 73. The derivative of any of claims 1 to 68 for the preparation of a medicament for the treatment of obesity. 74. Применение производного GLP-1 родительского пептида для получения лекарственного средства с пролонгированным профилем действия для лечения ожирения, где, по крайней мере, один аминокислотный остаток GLP-1 родительского пептида имеет липофильный заместитель, необязательно присоединенный через спейсер и где родительский пептид имеет в сумме до пятнадцати, предпочтительно до десяти аминокислотным остатков, замененных на любой α-аминокислотный остаток, который может быть кодирован с помощью генетического кода, при условии, что, если присутствует только один липофильный заместитель, и этот заместитель присоединен к N-концевому или С-концевому аминокислотному остатку родительского пептида, то этот заместитель является алкильной группой или группой, которая имеет ω-карбоксильную группу. 74. The use of the GLP-1 derivative of the parent peptide to produce a drug with a prolonged action profile for the treatment of obesity, where at least one amino acid residue GLP-1 of the parent peptide has a lipophilic substituent, optionally attached through a spacer, and where the parent peptide has in total up to fifteen, preferably up to ten amino acid residues, replaced by any α-amino acid residue that can be encoded using the genetic code, provided that, if It exists only one lipophilic substituent and this substituent is attached to the N-terminal or C-terminal amino acid residue of the parent peptide then this substituent is an alkyl group or a group which has the ω-carboxyl group.
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