RU2001102058A - Пролекарства ингибиторов дипептидилпептидазы iv - Google Patents
Пролекарства ингибиторов дипептидилпептидазы ivInfo
- Publication number
- RU2001102058A RU2001102058A RU2001102058/04A RU2001102058A RU2001102058A RU 2001102058 A RU2001102058 A RU 2001102058A RU 2001102058/04 A RU2001102058/04 A RU 2001102058/04A RU 2001102058 A RU2001102058 A RU 2001102058A RU 2001102058 A RU2001102058 A RU 2001102058A
- Authority
- RU
- Russia
- Prior art keywords
- prodrug compounds
- pharmaceutical composition
- treatment
- composition according
- preceding paragraphs
- Prior art date
Links
- 229940124213 Dipeptidyl peptidase 4 (DPP IV) inhibitor Drugs 0.000 title 1
- 239000003603 dipeptidyl peptidase IV inhibitor Substances 0.000 title 1
- 239000000651 prodrug Substances 0.000 claims 12
- 229940002612 prodrug Drugs 0.000 claims 12
- 150000001875 compounds Chemical class 0.000 claims 9
- 239000008194 pharmaceutical composition Substances 0.000 claims 6
- 230000005764 inhibitory process Effects 0.000 claims 5
- 206010012601 diabetes mellitus Diseases 0.000 claims 4
- 241000124008 Mammalia Species 0.000 claims 3
- 239000003112 inhibitor Substances 0.000 claims 3
- 208000010444 Acidosis Diseases 0.000 claims 2
- 208000007342 Diabetic Nephropathies Diseases 0.000 claims 2
- 208000032131 Diabetic Neuropathies Diseases 0.000 claims 2
- 208000002705 Glucose Intolerance Diseases 0.000 claims 2
- 206010018473 Glycosuria Diseases 0.000 claims 2
- PMMYEEVYMWASQN-DMTCNVIQSA-N Hydroxyproline Chemical group O[C@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-DMTCNVIQSA-N 0.000 claims 2
- 208000031226 Hyperlipidaemia Diseases 0.000 claims 2
- 206010027417 Metabolic acidosis Diseases 0.000 claims 2
- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 claims 2
- 150000001413 amino acids Chemical class 0.000 claims 2
- 210000004027 cell Anatomy 0.000 claims 2
- 208000033679 diabetic kidney disease Diseases 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 2
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 2
- PMMYEEVYMWASQN-UHFFFAOYSA-N dl-hydroxyproline Chemical group OC1C[NH2+]C(C([O-])=O)C1 PMMYEEVYMWASQN-UHFFFAOYSA-N 0.000 claims 2
- 239000003814 drug Substances 0.000 claims 2
- 230000000694 effects Effects 0.000 claims 2
- 230000035780 glucosuria Effects 0.000 claims 2
- 229960002591 hydroxyproline Drugs 0.000 claims 2
- 238000001727 in vivo Methods 0.000 claims 2
- 208000030159 metabolic disease Diseases 0.000 claims 2
- 210000000056 organ Anatomy 0.000 claims 2
- 201000009104 prediabetes syndrome Diseases 0.000 claims 2
- 125000001500 prolyl group Chemical group [H]N1C([H])(C(=O)[*])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims 2
- 210000001519 tissue Anatomy 0.000 claims 2
- FGMPLJWBKKVCDB-UHFFFAOYSA-N trans-L-hydroxy-proline Chemical group ON1CCCC1C(O)=O FGMPLJWBKKVCDB-UHFFFAOYSA-N 0.000 claims 2
- IADUEWIQBXOCDZ-VKHMYHEASA-N (S)-azetidine-2-carboxylic acid Chemical group OC(=O)[C@@H]1CCN1 IADUEWIQBXOCDZ-VKHMYHEASA-N 0.000 claims 1
- OMGHIGVFLOPEHJ-UHFFFAOYSA-N 2,5-dihydro-1h-pyrrol-1-ium-2-carboxylate Chemical group OC(=O)C1NCC=C1 OMGHIGVFLOPEHJ-UHFFFAOYSA-N 0.000 claims 1
- 108010016626 Dipeptides Proteins 0.000 claims 1
- 102000016622 Dipeptidyl Peptidase 4 Human genes 0.000 claims 1
- 101000930822 Giardia intestinalis Dipeptidyl-peptidase 4 Proteins 0.000 claims 1
- BBIXOODYWPFNDT-CIUDSAMLSA-N Ile-Pro Chemical compound CC[C@H](C)[C@H](N)C(=O)N1CCC[C@H]1C(O)=O BBIXOODYWPFNDT-CIUDSAMLSA-N 0.000 claims 1
- DZLNHFMRPBPULJ-VKHMYHEASA-N L-thioproline Chemical group OC(=O)[C@@H]1CSCN1 DZLNHFMRPBPULJ-VKHMYHEASA-N 0.000 claims 1
- KZNQNBZMBZJQJO-UHFFFAOYSA-N N-glycyl-L-proline Natural products NCC(=O)N1CCCC1C(O)=O KZNQNBZMBZJQJO-UHFFFAOYSA-N 0.000 claims 1
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 claims 1
- RLZXKARDPOFVNB-UHFFFAOYSA-N aziridine-1-carboxylic acid Chemical group OC(=O)N1CC1 RLZXKARDPOFVNB-UHFFFAOYSA-N 0.000 claims 1
- 210000004899 c-terminal region Anatomy 0.000 claims 1
- 239000012050 conventional carrier Substances 0.000 claims 1
- KZNQNBZMBZJQJO-YFKPBYRVSA-N glyclproline Chemical compound NCC(=O)N1CCC[C@H]1C(O)=O KZNQNBZMBZJQJO-YFKPBYRVSA-N 0.000 claims 1
- 108010077515 glycylproline Proteins 0.000 claims 1
- 108010031424 isoleucyl-prolyl-proline Proteins 0.000 claims 1
- HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Chemical group OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical group OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 claims 1
- 150000003839 salts Chemical class 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 230000036962 time dependent Effects 0.000 claims 1
Claims (17)
1. Соединения-пролекарства ингибиторов дипептидилпептидазы IV (ДП IV) общей формулы
А-В-С,
где А обозначает аминокислоту;
В обозначает химическую связь между А и С или аминокислоту;
С обозначает стабильный ингибитор ДП IV с отсутствующим С-концевым фосфонатным остатком.
2. Соединения-пролекарства по п.1, отличающиеся тем, что В представляет собой пролин, гидроксипролин, тиазолидинкарбоновую кислоту, дегидропролин, пипеколиновую кислоту, азетидинкарбоновую кислоту или азиридинкарбоновую кислоту.
3. Соединения-пролекарства по п.1 или 2, отличающиеся тем, что В представляет собой пролин, гидроксипролин.
4. Соединения-пролекарства по одному из предыдущих пунктов, отличающиеся тем, что С представляет собой аминоацилпирролидин, аминоацилтиазолидин или N-дипептидил, O-ацилгидроксиламин.
5. Соединения-пролекарства по одному из предыдущих пунктов, отличающиеся тем, что ингибиторы находятся в виде соли.
6. Соединения-пролекарства по одному из предыдущих пунктов, отличающиеся тем, что А-В представляет собой дипептид формулы Ile-Pro или Gly-Pro.
7. Фармацевтическая композиция, в частности, для перорального введения, отличающаяся тем, что она содержит по меньшей мере одно соединение-пролекарство по одному из предыдущих пунктов в случае необходимости в комбинации с обычными носителями или вспомогательными веществами.
8. Соединения-пролекарства по одному из пп.1-6 для приготовления лекарственного средства для регулируемого во времени ингибирования in vivo ДП IV.
9. Соединения-пролекарства по одному из пп.1-6 для клеточного, тканевого или органоспецифического ингибирования ДП IV.
10. Соединения-пролекарства по одному из пп.1-6 для лечения заболеваний млекопитающих, излечиваемых модуляцией ДП IV-активности.
11. Соединения-пролекарства по п.9 для лечения обменных заболеваний людей.
12. Соединения-пролекарства по п.9 для лечения нарушенной толерантности к глюкозе, глюкозурии, гиперлипидемии, метаболических ацидозов, сахарного диабета, диабетической невропатии и нефропатии, а также обусловленных сахарным диабетом осложнений млекопитающих.
13. Фармацевтическая композиция по п.7 для приготовления лекарственного средства для регулируемого во времени ингибирования in vivo ДП IV.
14. Фармацевтическая композиция по п.7 для клеточного, тканевого или органоспецифического ингибирования ДП IV.
15. Фармацевтическая композиция по п.7 для лечения заболеваний млекопитающих, излечиваемых модуляцией ДП IV-активности.
16. Фармацевтическая композиция по п.9 для лечения обменных заболеваний людей.
17. Фармацевтическая композиция по п.9 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 |
|---|---|---|---|
| DE19828113.7 | 1998-06-24 | ||
| DE19828113A DE19828113A1 (de) | 1998-06-24 | 1998-06-24 | Prodrugs von Inhibitoren der Dipeptidyl Peptidase IV |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2003136759/04A Division RU2003136759A (ru) | 1998-06-24 | 2003-12-18 | Пролекарства ингибиторов дипептидилпептидазы iv |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2001102058A true RU2001102058A (ru) | 2003-07-20 |
| RU2226533C2 RU2226533C2 (ru) | 2004-04-10 |
Family
ID=7871859
Family Applications (2)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2001102058/04A RU2226533C2 (ru) | 1998-06-24 | 1999-06-24 | Пролекарства ингибиторов дипептидилпептидазы iv |
| RU2003136759/04A RU2003136759A (ru) | 1998-06-24 | 2003-12-18 | Пролекарства ингибиторов дипептидилпептидазы iv |
Family Applications After (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2003136759/04A RU2003136759A (ru) | 1998-06-24 | 2003-12-18 | Пролекарства ингибиторов дипептидилпептидазы iv |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US7084120B2 (ru) |
| EP (1) | EP1087991B1 (ru) |
| JP (1) | JP4088419B2 (ru) |
| KR (1) | KR100529816B1 (ru) |
| CN (1) | CN1245417C (ru) |
| AT (1) | ATE441660T1 (ru) |
| AU (1) | AU766726C (ru) |
| BR (1) | BR9911468A (ru) |
| CA (1) | CA2335992A1 (ru) |
| DE (2) | DE19828113A1 (ru) |
| HU (1) | HUP0102281A3 (ru) |
| IL (1) | IL140336A0 (ru) |
| NO (1) | NO20006484L (ru) |
| NZ (1) | NZ508722A (ru) |
| PL (1) | PL345151A1 (ru) |
| RU (2) | RU2226533C2 (ru) |
| WO (1) | WO1999067278A1 (ru) |
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-
1998
- 1998-06-24 DE DE19828113A patent/DE19828113A1/de not_active Ceased
-
1999
- 1999-06-24 AT AT99932721T patent/ATE441660T1/de not_active IP Right Cessation
- 1999-06-24 CA CA002335992A patent/CA2335992A1/en not_active Abandoned
- 1999-06-24 CN CNB998076295A patent/CN1245417C/zh not_active Expired - Fee Related
- 1999-06-24 NZ NZ508722A patent/NZ508722A/en unknown
- 1999-06-24 AU AU49007/99A patent/AU766726C/en not_active Ceased
- 1999-06-24 BR BR9911468-2A patent/BR9911468A/pt not_active IP Right Cessation
- 1999-06-24 RU RU2001102058/04A patent/RU2226533C2/ru not_active IP Right Cessation
- 1999-06-24 EP EP99932721A patent/EP1087991B1/de not_active Expired - Lifetime
- 1999-06-24 DE DE59915073T patent/DE59915073D1/de not_active Expired - Fee Related
- 1999-06-24 JP JP2000555929A patent/JP4088419B2/ja not_active Expired - Fee Related
- 1999-06-24 HU HU0102281A patent/HUP0102281A3/hu unknown
- 1999-06-24 IL IL14033699A patent/IL140336A0/xx unknown
- 1999-06-24 WO PCT/EP1999/004382 patent/WO1999067278A1/de not_active Ceased
- 1999-06-24 PL PL99345151A patent/PL345151A1/xx not_active Application Discontinuation
- 1999-06-24 KR KR10-2000-7014662A patent/KR100529816B1/ko not_active Expired - Fee Related
-
2000
- 2000-12-19 NO NO20006484A patent/NO20006484L/no not_active Application Discontinuation
- 2000-12-22 US US09/745,776 patent/US7084120B2/en not_active Expired - Fee Related
-
2003
- 2003-12-11 US US10/735,582 patent/US7166579B2/en not_active Expired - Lifetime
- 2003-12-18 RU RU2003136759/04A patent/RU2003136759A/ru not_active Application Discontinuation
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