NO321664B1 - N-heterosykliske derivater som NOS-inhibitorer - Google Patents
N-heterosykliske derivater som NOS-inhibitorer Download PDFInfo
- Publication number
- NO321664B1 NO321664B1 NO19993996A NO993996A NO321664B1 NO 321664 B1 NO321664 B1 NO 321664B1 NO 19993996 A NO19993996 A NO 19993996A NO 993996 A NO993996 A NO 993996A NO 321664 B1 NO321664 B1 NO 321664B1
- Authority
- NO
- Norway
- Prior art keywords
- formula
- compound according
- imidazol
- hydrogen
- alkyl
- Prior art date
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- 239000003112 inhibitor Substances 0.000 title abstract description 11
- 150000001875 compounds Chemical class 0.000 claims abstract description 255
- 239000001257 hydrogen Substances 0.000 claims description 52
- 229910052739 hydrogen Inorganic materials 0.000 claims description 52
- MWUXSHHQAYIFBG-UHFFFAOYSA-N Nitric oxide Chemical compound O=[N] MWUXSHHQAYIFBG-UHFFFAOYSA-N 0.000 claims description 46
- -1 anisyl Chemical group 0.000 claims description 45
- 239000000460 chlorine Substances 0.000 claims description 37
- 150000002431 hydrogen Chemical class 0.000 claims description 28
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
- 239000000203 mixture Substances 0.000 claims description 23
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
- 238000011282 treatment Methods 0.000 claims description 17
- 125000000217 alkyl group Chemical group 0.000 claims description 16
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 13
- 229910052736 halogen Inorganic materials 0.000 claims description 12
- 150000002367 halogens Chemical class 0.000 claims description 12
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 238000004519 manufacturing process Methods 0.000 claims description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
- 125000004193 piperazinyl group Chemical group 0.000 claims description 8
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 8
- 229910052757 nitrogen Inorganic materials 0.000 claims description 7
- 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
- 230000005856 abnormality Effects 0.000 claims description 6
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000003386 piperidinyl group Chemical group 0.000 claims description 6
- 208000001953 Hypotension Diseases 0.000 claims description 5
- 230000036543 hypotension Effects 0.000 claims description 5
- IMRLNKLOSQHNRT-UHFFFAOYSA-N n-(1,3-benzodioxol-5-ylmethyl)-2-[1-(2-imidazol-1-ylpyrimidin-4-yl)piperidin-2-yl]ethanamine Chemical compound C=1C=C2OCOC2=CC=1CNCCC1CCCCN1C(N=1)=CC=NC=1N1C=CN=C1 IMRLNKLOSQHNRT-UHFFFAOYSA-N 0.000 claims description 5
- 206010001052 Acute respiratory distress syndrome Diseases 0.000 claims description 4
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- 206010040070 Septic Shock Diseases 0.000 claims description 4
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 claims description 4
- 125000000068 chlorophenyl group Chemical group 0.000 claims description 4
- 125000005805 dimethoxy phenyl group Chemical group 0.000 claims description 4
- 125000005842 heteroatom Chemical group 0.000 claims description 4
- 125000002883 imidazolyl group Chemical group 0.000 claims description 4
- 230000002401 inhibitory effect Effects 0.000 claims description 4
- 230000001404 mediated effect Effects 0.000 claims description 4
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- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 4
- 125000004568 thiomorpholinyl group Chemical group 0.000 claims description 4
- 125000003944 tolyl group Chemical group 0.000 claims description 4
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- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 2
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 2
- 125000006528 (C2-C6) alkyl group Chemical group 0.000 claims description 2
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 2
- BXPFAYHUZWALPV-UHFFFAOYSA-N 1-(2-imidazol-1-yl-6-methylpyrimidin-4-yl)-n-[2-(4-methoxyphenyl)ethyl]pyrrolidine-2-carboxamide Chemical compound C1=CC(OC)=CC=C1CCNC(=O)C1N(C=2N=C(N=C(C)C=2)N2C=NC=C2)CCC1 BXPFAYHUZWALPV-UHFFFAOYSA-N 0.000 claims description 2
- JWXNMIUXCQSJPN-UHFFFAOYSA-N 2-[1-(2-imidazol-1-ylpyrimidin-4-yl)piperidin-2-yl]-n-[(3-methoxyphenyl)methyl]acetamide Chemical compound COC1=CC=CC(CNC(=O)CC2N(CCCC2)C=2N=C(N=CC=2)N2C=NC=C2)=C1 JWXNMIUXCQSJPN-UHFFFAOYSA-N 0.000 claims description 2
- KRNSTVMZJJNREA-UHFFFAOYSA-N 2-[1-(2-imidazol-1-ylpyrimidin-4-yl)piperidin-2-yl]-n-[2-(4-methoxyphenyl)ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1CCNC(=O)CC1N(C=2N=C(N=CC=2)N2C=NC=C2)CCCC1 KRNSTVMZJJNREA-UHFFFAOYSA-N 0.000 claims description 2
- FWWGWXJYUJMNDW-UHFFFAOYSA-N 2-[1-(6-chloro-2-imidazol-1-ylpyrimidin-4-yl)-4-methylsulfonylpiperazin-2-yl]-n-[(3-chloro-4-methoxyphenyl)methyl]acetamide Chemical compound C1=C(Cl)C(OC)=CC=C1CNC(=O)CC1N(C=2N=C(N=C(Cl)C=2)N2C=NC=C2)CCN(S(C)(=O)=O)C1 FWWGWXJYUJMNDW-UHFFFAOYSA-N 0.000 claims description 2
- NINRLNOCFRXTQW-UHFFFAOYSA-N 2-[1-[2-(2-imidazol-1-ylethyl)-6-methylpyrimidin-4-yl]piperidin-2-yl]-n-(2-morpholin-4-ylethyl)acetamide Chemical compound N=1C(C)=CC(N2C(CCCC2)CC(=O)NCCN2CCOCC2)=NC=1CCN1C=CN=C1 NINRLNOCFRXTQW-UHFFFAOYSA-N 0.000 claims description 2
- LTRMEZVTPLMITR-UHFFFAOYSA-N 2-[1-acetyl-4-(6-chloro-2-imidazol-1-ylpyrimidin-4-yl)piperazin-2-yl]-n-(1,3-benzodioxol-5-ylmethyl)acetamide Chemical compound C1C(CC(=O)NCC=2C=C3OCOC3=CC=2)N(C(=O)C)CCN1C(N=1)=CC(Cl)=NC=1N1C=CN=C1 LTRMEZVTPLMITR-UHFFFAOYSA-N 0.000 claims description 2
- BKTJUPLIDGRAIT-UHFFFAOYSA-N 2-[4-(2-imidazol-1-yl-6-methylpyrimidin-4-yl)thiomorpholin-2-yl]-n-[2-(4-methoxyphenyl)ethyl]acetamide Chemical compound C1=CC(OC)=CC=C1CCNC(=O)CC1SCCN(C=2N=C(N=C(C)C=2)N2C=NC=C2)C1 BKTJUPLIDGRAIT-UHFFFAOYSA-N 0.000 claims description 2
- 125000003762 3,4-dimethoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C(OC([H])([H])[H])C([H])=C1* 0.000 claims description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 2
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- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 2
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- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
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- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
- ZDXMIBCVFUNDDW-UHFFFAOYSA-N methyl 2-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-4-(2-imidazol-1-yl-6-methoxypyrimidin-4-yl)piperazine-1-carboxylate Chemical compound C1C(CC(=O)NCC=2C=C3OCOC3=CC=2)N(C(=O)OC)CCN1C(N=1)=CC(OC)=NC=1N1C=CN=C1 ZDXMIBCVFUNDDW-UHFFFAOYSA-N 0.000 claims description 2
- NVYMEDQKBQMAKF-UHFFFAOYSA-N methyl 3-[2-(1,3-benzodioxol-5-ylmethylamino)-2-oxoethyl]-4-(2-imidazol-1-ylpyrimidin-4-yl)piperazine-1-carboxylate Chemical compound C=1C=C2OCOC2=CC=1CNC(=O)CC1CN(C(=O)OC)CCN1C(N=1)=CC=NC=1N1C=CN=C1 NVYMEDQKBQMAKF-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D233/00—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings
- C07D233/54—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members
- C07D233/56—Heterocyclic compounds containing 1,3-diazole or hydrogenated 1,3-diazole rings, not condensed with other rings having two double bonds between ring members or between ring members and non-ring members with only hydrogen atoms or radicals containing only hydrogen and carbon atoms, attached to ring carbon atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D249/00—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms
- C07D249/02—Heterocyclic compounds containing five-membered rings having three nitrogen atoms as the only ring hetero atoms not condensed with other rings
- C07D249/08—1,2,4-Triazoles; Hydrogenated 1,2,4-triazoles
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- Health & Medical Sciences (AREA)
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- Chemical & Material Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
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- Heart & Thoracic Surgery (AREA)
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- Transplantation (AREA)
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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US80897597A | 1997-02-19 | 1997-02-19 | |
| US2512498A | 1998-02-17 | 1998-02-17 | |
| PCT/US1998/003176 WO1998037079A1 (fr) | 1997-02-19 | 1998-02-19 | Derives n-heterocycliques utiles en tant qu'inhibiteurs de la no synthetase |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| NO993996D0 NO993996D0 (no) | 1999-08-19 |
| NO993996L NO993996L (no) | 1999-10-18 |
| NO321664B1 true NO321664B1 (no) | 2006-06-19 |
Family
ID=26699322
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| NO19993996A NO321664B1 (no) | 1997-02-19 | 1999-08-19 | N-heterosykliske derivater som NOS-inhibitorer |
Country Status (21)
| Country | Link |
|---|---|
| EP (2) | EP1754703A3 (fr) |
| JP (1) | JP4495257B2 (fr) |
| KR (1) | KR20000075615A (fr) |
| CN (1) | CN1100777C (fr) |
| AT (1) | ATE345339T1 (fr) |
| AU (1) | AU732969B2 (fr) |
| CA (1) | CA2281545C (fr) |
| CZ (1) | CZ2008628A3 (fr) |
| DE (1) | DE69836422T2 (fr) |
| DK (1) | DK0968206T3 (fr) |
| ES (1) | ES2277382T3 (fr) |
| GB (1) | GB2338957B (fr) |
| HK (1) | HK1025952A1 (fr) |
| IL (1) | IL131475A0 (fr) |
| NO (1) | NO321664B1 (fr) |
| NZ (1) | NZ337861A (fr) |
| PL (1) | PL335235A1 (fr) |
| PT (1) | PT968206E (fr) |
| RU (1) | RU2241708C2 (fr) |
| SK (1) | SK286779B6 (fr) |
| WO (1) | WO1998037079A1 (fr) |
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| WO2001027091A1 (fr) | 1999-10-08 | 2001-04-19 | Du Pont Pharmaceuticals Company | AMINO SULFONAMIDES DE LACTAME UTILISES COMME INHIBITEURS DE LA PRODUCTION DE PROTEINE A$g(b) |
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| US6525051B2 (en) * | 2000-03-27 | 2003-02-25 | Schering Aktiengesellschaft | N-heterocyclic derivatives as NOS inhibitors |
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| BR0107532A (pt) | 2000-04-03 | 2004-11-03 | Bristol Myers Squibb Pharma Co | Composto, uso do composto, método para o tratamento de disfunções neurológicas associadas com a produção de b-amilóide, método de inibição da atividade de y-secretase e composição farmacêutica |
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| US20030055249A1 (en) * | 2001-07-17 | 2003-03-20 | Fick David B. | Synthesis and methods of use of pyrimidine analogues and derivatives |
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| BR0212787A (pt) * | 2001-09-24 | 2005-01-25 | Elan Pharm Inc | Composto ou sal farmaceuticamente aceitável do mesmo, métodos de tratamento ou prevenção de doenças e de preparação de um composto, uso de um composto ou sal, e, composição farmacêutica |
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| KR20150098605A (ko) | 2012-12-21 | 2015-08-28 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 퀴놀린 유도체의 비정질 형태 및 그의 제조방법 |
| LT2970218T (lt) | 2013-03-12 | 2019-03-12 | Vertex Pharmaceuticals Incorporated | Dna-pk inhibitoriai |
| JP6411379B2 (ja) | 2013-05-14 | 2018-10-24 | エーザイ・アール・アンド・ディー・マネジメント株式会社 | レンバチニブ化合物に対する子宮内膜がん対象の応答性を予測及び評価するためのバイオマーカー |
| SG11201602962PA (en) | 2013-10-17 | 2016-05-30 | Vertex Pharma | Co-crystals of (s)-n-methyl-8-(1-((2'-methyl-[4,5'-bipyrimidin]-6-yl)amino)propan-2-yl)quinoline-4-carboxamide and deuterated derivatives thereof as dna-pk inhibitors |
| US10258621B2 (en) | 2014-07-17 | 2019-04-16 | Chdi Foundation, Inc. | Methods and compositions for treating HIV-related disorders |
| ES2926687T3 (es) | 2014-08-28 | 2022-10-27 | Eisai R&D Man Co Ltd | Derivado de quinolina muy puro y método para su producción |
| US20180028662A1 (en) | 2015-02-25 | 2018-02-01 | Eisai R&D Management Co., Ltd. | Method for Suppressing Bitterness of Quinoline Derivative |
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| CA2988707C (fr) | 2015-06-16 | 2023-10-10 | Eisai R&D Management Co., Ltd. | Combinaison de proteine se liant au cre/inhibiteur de catenine et d'un inhibiteur de point de controle immunitaire servant au traitement du cancer |
| US20200377481A1 (en) * | 2016-06-07 | 2020-12-03 | Northwestern University | Substituted 4-(1-pyrrolidinyl)pyrimidine compounds as dimerization inhibitors of neuronal nitric oxide synthase |
| KR20190062485A (ko) | 2016-09-27 | 2019-06-05 | 버텍스 파마슈티칼스 인코포레이티드 | Dna-손상제 및 dna-pk 저해제의 조합을 사용한 암 치료 방법 |
| RU2732297C2 (ru) * | 2018-11-14 | 2020-09-15 | Общество с ограниченной ответственностью "Гурус БиоФарм" | Производные нестероидных противовоспалительных средств |
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| JPS6339875A (ja) * | 1986-08-05 | 1988-02-20 | Nissin Food Prod Co Ltd | ピリミジン誘導体 |
| DK0640599T3 (da) * | 1993-08-26 | 1998-09-28 | Ono Pharmaceutical Co | 4-Aminopyrimidin-derivater |
-
1998
- 1998-02-19 AT AT98906555T patent/ATE345339T1/de not_active IP Right Cessation
- 1998-02-19 RU RU99120077/04A patent/RU2241708C2/ru active
- 1998-02-19 GB GB9919686A patent/GB2338957B/en not_active Expired - Fee Related
- 1998-02-19 NZ NZ337861A patent/NZ337861A/xx unknown
- 1998-02-19 CA CA002281545A patent/CA2281545C/fr not_active Expired - Fee Related
- 1998-02-19 CN CN98804281A patent/CN1100777C/zh not_active Expired - Fee Related
- 1998-02-19 JP JP53685398A patent/JP4495257B2/ja not_active Expired - Fee Related
- 1998-02-19 PL PL98335235A patent/PL335235A1/xx not_active Application Discontinuation
- 1998-02-19 DK DK98906555T patent/DK0968206T3/da active
- 1998-02-19 PT PT98906555T patent/PT968206E/pt unknown
- 1998-02-19 EP EP06023449A patent/EP1754703A3/fr not_active Withdrawn
- 1998-02-19 WO PCT/US1998/003176 patent/WO1998037079A1/fr active Application Filing
- 1998-02-19 EP EP98906555A patent/EP0968206B8/fr not_active Expired - Lifetime
- 1998-02-19 KR KR1019997007678A patent/KR20000075615A/ko not_active Application Discontinuation
- 1998-02-19 IL IL13147598A patent/IL131475A0/xx not_active IP Right Cessation
- 1998-02-19 CZ CZ2008-628A patent/CZ2008628A3/cs unknown
- 1998-02-19 DE DE69836422T patent/DE69836422T2/de not_active Expired - Lifetime
- 1998-02-19 AU AU61749/98A patent/AU732969B2/en not_active Ceased
- 1998-02-19 ES ES98906555T patent/ES2277382T3/es not_active Expired - Lifetime
- 1998-02-19 SK SK1135-99A patent/SK286779B6/sk not_active IP Right Cessation
-
1999
- 1999-08-19 NO NO19993996A patent/NO321664B1/no not_active IP Right Cessation
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2000
- 2000-07-11 HK HK00104236A patent/HK1025952A1/xx not_active IP Right Cessation
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