RU2226195C2 - Соединения нестабильных ингибиторов дипептидилпептидазы iv - Google Patents
Соединения нестабильных ингибиторов дипептидилпептидазы iv Download PDFInfo
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- RU2226195C2 RU2226195C2 RU2001102057/04A RU2001102057A RU2226195C2 RU 2226195 C2 RU2226195 C2 RU 2226195C2 RU 2001102057/04 A RU2001102057/04 A RU 2001102057/04A RU 2001102057 A RU2001102057 A RU 2001102057A RU 2226195 C2 RU2226195 C2 RU 2226195C2
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K5/00—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof
- C07K5/04—Peptides containing up to four amino acids in a fully defined sequence; Derivatives thereof containing only normal peptide links
- C07K5/08—Tripeptides
- C07K5/0802—Tripeptides with the first amino acid being neutral
- C07K5/0804—Tripeptides with the first amino acid being neutral and aliphatic
- C07K5/0808—Tripeptides with the first amino acid being neutral and aliphatic the side chain containing 2 to 4 carbon atoms, e.g. Val, Ile, Leu
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/06—Antihyperlipidemics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P3/00—Drugs for disorders of the metabolism
- A61P3/08—Drugs for disorders of the metabolism for glucose homeostasis
- A61P3/10—Drugs for disorders of the metabolism for glucose homeostasis for hyperglycaemia, e.g. antidiabetics
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Abstract
Изобретение относится к соединениям нестабильных ингибиторов дипептидилпептидазы IV (ДП IV), которые имеют общую формулу А-В-С, где А обозначает аминокислоту, В обозначает химическую связь между А и С или аминокислоту и С обозначает нестабильный ингибитор ДП IV, а именно производное дипептидилалкилкетона, за исключением производного фторалкилкетона в качестве производного дипептидилалкилкетона, остаток дипептидилхлоралкилкетона, дипептидилцианида или дипептидилпиридинийметилкетона. Технический результат: повышение стабильности ингибиторов дипептидилпептидазы IV, возможность регулирования начала действия и продолжительности действия. Подобные соединения применяются для лечения нарушенной толерантности к глюкозе, глюкозурии, гиперлипидемии, метаболических ацидозов, сахарного диабета, диабетической невропатии и нефропатии, а также обусловленных сахарным диабетом осложнений млекопитающих. Описаны также фармацевтические композиции, содержащие такие соединения. 2 с. и 16 з.п. ф-лы, 8 ил., 2 табл.
Description
Текст описания в факсимильном виде (см. графическую часть).
Claims (18)
1. Соединения ингибиторов дипептидилпептидазы IV (ДП IV) общей формулы А-В-С, при этом А обозначает аминокислоту, В обозначает химическую связь между А и С или аминокислоту и С обозначает нестабильный ингибитор ДП IV, а именно производное дипептидилалкилкетона, за исключением производного фторалкилкетона в качестве производного дипептидилалкилкетона, а также остатки дипептидилхлоралкилкетона, дипептидилцианида или дипептидилпиридинийметилкетона.
2. Соединения по п.1, отличающиеся тем, что В представляет собой пролин, гидроксипролин, тиазолидинкарбоновую кислоту, дегидропролин, пипеколиновую кислоту, азетидинкарбоновую кислоту или азиридинкарбоновую кислоту.
3. Соединения по п.1 или 2, отличающиеся тем, что В представляет собой пролин или гидроксипролин.
4. Соединения по одному из предыдущих пунктов, отличающиеся тем, что дипептидная группа представляет собой Ile-Thia, Ile-Pyr, Val-Thia или Val-Pyr.
5. Соединения по одному из предыдущих пунктов, отличающиеся тем, что ингибиторы находятся в форме соли.
6. Соединения по одному из предыдущих пунктов, отличающиеся тем, что ингибиторы находятся в виде органических солей, таких, как ацетат, сукцинат, тартрат или фумарат, или в виде неорганических кислотных остатков, таких, как фосфат или сульфат.
7. Соединения по одному из предыдущих пунктов, отличающиеся тем, что А-В представляет собой дипептид формулы Ile-Pro или Gly-Pro.
8. Фармацевтическая композиция, обладающая ингибирующей активностью по отношению к дипептидилпептидазе IV, отличающаяся тем, что она содержит по меньшей мере одно соединение по одному из предыдущих пунктов в случае необходимости в комбинации с обычными носителями или вспомогательными веществами.
9. Соединения по одному из пп.1-7 для приготовления лекарственного средства для регулируемого во времени ингибирования in vivo ДП IV.
10. Соединения по одному из пп.1-7 для клеточного тканевого или органоспецифического ингибирования ДП IV.
11. Соединения по одному из пп.1-7 для лечения заболеваний млекопитающих, излечиваемых модуляцией ДП IV-активности.
12. Соединения по п.10 для лечения обменных заболеваний людей.
13. Соединения по п.10 для лечения нарушенной толерантности к глюкозе, глюкозурии, гиперлипидемии, метаболических ацидозов, сахарного диабета, диабетической невропатии и нефропатии, а также обусловленных сахарным диабетом осложнений млекопитающих.
14. Фармацевтическая композиция по п.8 для регулируемого по времени ингибирования in vivo ДП IV.
15. Фармацевтическая композиция по п.8 для клеточного тканевого или органоспецифического ингибирования ДП - IV.
16. Фармацевтическая композиция по п.8 для лечения заболеваний млекопитающих, излечиваемых модуляцией ДП IV-активности.
17. Фармацевтическая композиция по п.15 для лечения обменных заболеваний людей.
18. Фармацевтическая композиция по п.15 для лечения нарушенной толерантности к глюкозе, глюкозурии, гиперлипидемии, метаболических ацидозов, сахарного диабета, диабетической невропатии и нефропатии, а также обусловленных сахарным диабетом осложнений млекопитающих.
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE19828114.5 | 1998-06-24 | ||
DE19828114A DE19828114A1 (de) | 1998-06-24 | 1998-06-24 | Produgs instabiler Inhibitoren der Dipeptidyl Peptidase IV |
Publications (2)
Publication Number | Publication Date |
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RU2001102057A RU2001102057A (ru) | 2003-07-20 |
RU2226195C2 true RU2226195C2 (ru) | 2004-03-27 |
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Application Number | Title | Priority Date | Filing Date |
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RU2001102057/04A RU2226195C2 (ru) | 1998-06-24 | 1999-06-24 | Соединения нестабильных ингибиторов дипептидилпептидазы iv |
Country Status (17)
Country | Link |
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US (1) | US7053055B2 (ru) |
EP (1) | EP1090030A1 (ru) |
JP (1) | JP3761781B2 (ru) |
KR (1) | KR100630254B1 (ru) |
CN (1) | CN100345866C (ru) |
AU (1) | AU758843B2 (ru) |
BR (1) | BR9911415A (ru) |
CA (1) | CA2335978A1 (ru) |
DE (1) | DE19828114A1 (ru) |
HU (1) | HUP0102250A3 (ru) |
IL (1) | IL140338A0 (ru) |
IS (1) | IS5739A (ru) |
NO (1) | NO20006483L (ru) |
NZ (1) | NZ508721A (ru) |
PL (1) | PL345060A1 (ru) |
RU (1) | RU2226195C2 (ru) |
WO (1) | WO1999067279A1 (ru) |
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CN100345866C (zh) | 2007-10-31 |
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KR100630254B1 (ko) | 2006-10-02 |
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DE19828114A1 (de) | 2000-01-27 |
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JP2002518518A (ja) | 2002-06-25 |
NO20006483L (no) | 2000-12-19 |
HUP0102250A2 (hu) | 2001-11-28 |
CA2335978A1 (en) | 1999-12-29 |
AU758843B2 (en) | 2003-04-03 |
HUP0102250A3 (en) | 2001-12-28 |
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