RU2091374C1 - Способ получения замещенных 5-арил-пиримидинов - Google Patents
Способ получения замещенных 5-арил-пиримидинов Download PDFInfo
- Publication number
- RU2091374C1 RU2091374C1 SU914895583A SU4895583A RU2091374C1 RU 2091374 C1 RU2091374 C1 RU 2091374C1 SU 914895583 A SU914895583 A SU 914895583A SU 4895583 A SU4895583 A SU 4895583A RU 2091374 C1 RU2091374 C1 RU 2091374C1
- Authority
- RU
- Russia
- Prior art keywords
- amino
- pyrimidine
- trichlorophenyl
- piperazinyl
- dichlorophenyl
- Prior art date
Links
- 238000000034 method Methods 0.000 title claims description 35
- 150000001875 compounds Chemical class 0.000 claims abstract description 122
- 150000003839 salts Chemical class 0.000 claims abstract description 47
- 238000006243 chemical reaction Methods 0.000 claims abstract description 27
- 239000012458 free base Substances 0.000 claims abstract description 14
- 125000006239 protecting group Chemical group 0.000 claims abstract description 7
- CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 claims abstract description 6
- YJQWLFUYDVSUEX-UHFFFAOYSA-N 5-(3,5-dichlorophenyl)-6-(trifluoromethyl)pyrimidine-2,4-diamine Chemical compound FC(F)(F)C1=NC(N)=NC(N)=C1C1=CC(Cl)=CC(Cl)=C1 YJQWLFUYDVSUEX-UHFFFAOYSA-N 0.000 claims abstract description 5
- -1 4-iodo-2,3,5-trichlorophenyl Chemical group 0.000 claims description 62
- ZYSMJCDSMWNIQQ-UHFFFAOYSA-N 3-methoxy-2-(2,3,5-trichlorophenyl)prop-2-enenitrile Chemical compound COC=C(C#N)C1=CC(Cl)=CC(Cl)=C1Cl ZYSMJCDSMWNIQQ-UHFFFAOYSA-N 0.000 claims description 8
- WJJDXHHPQMNMHX-UHFFFAOYSA-N 5-(4-amino-2,3,5-trichlorophenyl)pyrimidine-2,4-diamine Chemical compound NC1=NC(N)=NC=C1C1=CC(Cl)=C(N)C(Cl)=C1Cl WJJDXHHPQMNMHX-UHFFFAOYSA-N 0.000 claims description 7
- TUQWAURGVMOVKD-UHFFFAOYSA-N 5-(3,5-dichlorophenyl)-2-(4-methylpiperazin-1-yl)pyrimidin-4-amine Chemical compound C1CN(C)CCN1C1=NC=C(C=2C=C(Cl)C=C(Cl)C=2)C(N)=N1 TUQWAURGVMOVKD-UHFFFAOYSA-N 0.000 claims description 6
- NWAGOKSOHKBDPE-UHFFFAOYSA-N 5-(4-amino-3,5-dichlorophenyl)pyrimidine-2,4-diamine Chemical compound NC1=NC(N)=NC=C1C1=CC(Cl)=C(N)C(Cl)=C1 NWAGOKSOHKBDPE-UHFFFAOYSA-N 0.000 claims description 6
- VFQQXOLBMUZRLB-UHFFFAOYSA-N 2-(4-ethylpiperazin-1-yl)-5-(2,3,5-trichlorophenyl)pyrimidin-4-amine Chemical compound C1CN(CC)CCN1C1=NC=C(C=2C(=C(Cl)C=C(Cl)C=2)Cl)C(N)=N1 VFQQXOLBMUZRLB-UHFFFAOYSA-N 0.000 claims description 5
- RZABVGKFPFSKJP-UHFFFAOYSA-N 2-(4-benzylpiperazin-1-yl)-5-(2,3,5-trichlorophenyl)pyrimidin-4-amine Chemical compound NC1=NC(N2CCN(CC=3C=CC=CC=3)CC2)=NC=C1C1=CC(Cl)=CC(Cl)=C1Cl RZABVGKFPFSKJP-UHFFFAOYSA-N 0.000 claims description 4
- MQRADWWRHVBWHX-UHFFFAOYSA-N 2-(4-propylpiperazin-1-yl)-5-(2,3,5-trichlorophenyl)pyrimidin-4-amine Chemical compound C1CN(CCC)CCN1C1=NC=C(C=2C(=C(Cl)C=C(Cl)C=2)Cl)C(N)=N1 MQRADWWRHVBWHX-UHFFFAOYSA-N 0.000 claims description 4
- KXXCUIBIORBOGC-UHFFFAOYSA-N 5-(4-amino-3,5-dichlorophenyl)-6-(trifluoromethyl)pyrimidine-2,4-diamine Chemical compound FC(F)(F)C1=NC(N)=NC(N)=C1C1=CC(Cl)=C(N)C(Cl)=C1 KXXCUIBIORBOGC-UHFFFAOYSA-N 0.000 claims description 4
- FWJSVGUOJIKCLH-UHFFFAOYSA-N 2-(4-butylpiperazin-1-yl)-5-(2,3,5-trichlorophenyl)pyrimidin-4-amine Chemical compound C1CN(CCCC)CCN1C1=NC=C(C=2C(=C(Cl)C=C(Cl)C=2)Cl)C(N)=N1 FWJSVGUOJIKCLH-UHFFFAOYSA-N 0.000 claims description 3
- AOQBUGMDTINKNL-UHFFFAOYSA-N 2-(4-cyclopropylpiperazin-1-yl)-5-(2,3,5-trichlorophenyl)pyrimidin-4-amine Chemical compound NC1=NC(N2CCN(CC2)C2CC2)=NC=C1C1=CC(Cl)=CC(Cl)=C1Cl AOQBUGMDTINKNL-UHFFFAOYSA-N 0.000 claims description 3
- XYMFQPCVHNYLAW-UHFFFAOYSA-N 2-n,2-n-diethyl-5-(2,3,5-trichlorophenyl)pyrimidine-2,4-diamine Chemical compound NC1=NC(N(CC)CC)=NC=C1C1=CC(Cl)=CC(Cl)=C1Cl XYMFQPCVHNYLAW-UHFFFAOYSA-N 0.000 claims description 3
- DTUHEHSZZIELQD-UHFFFAOYSA-N 5-(3,5-dichlorophenyl)-2-(4-ethylpiperazin-1-yl)-6-(trifluoromethyl)pyrimidin-4-amine Chemical compound C1CN(CC)CCN1C(N=C1C(F)(F)F)=NC(N)=C1C1=CC(Cl)=CC(Cl)=C1 DTUHEHSZZIELQD-UHFFFAOYSA-N 0.000 claims description 3
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- 125000003545 alkoxy group Chemical group 0.000 claims description 3
- SRSZUNLFCXBZCK-UHFFFAOYSA-N 5-(3,5-dichlorophenyl)-2-(4-propan-2-ylpiperazin-1-yl)-6-(trifluoromethyl)pyrimidin-4-amine Chemical compound C1CN(C(C)C)CCN1C(N=C1C(F)(F)F)=NC(N)=C1C1=CC(Cl)=CC(Cl)=C1 SRSZUNLFCXBZCK-UHFFFAOYSA-N 0.000 claims description 2
- KULFIMRKKQDMMW-UHFFFAOYSA-N 5-(3,5-dichlorophenyl)-6-(methoxymethyl)-2-(4-methylpiperazin-1-yl)pyrimidin-4-amine Chemical compound COCC1=NC(N2CCN(C)CC2)=NC(N)=C1C1=CC(Cl)=CC(Cl)=C1 KULFIMRKKQDMMW-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
- C07D239/49—Two nitrogen atoms with an aralkyl radical, or substituted aralkyl radical, attached in position 5, e.g. trimethoprim
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/48—Two nitrogen atoms
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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
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- 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
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Liquid Crystal Substances (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
- Paper (AREA)
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GB90123167 | 1990-06-01 | ||
| GB909012316A GB9012316D0 (en) | 1990-06-01 | 1990-06-01 | Pharmacologically active cns compounds |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| RU2091374C1 true RU2091374C1 (ru) | 1997-09-27 |
Family
ID=10676964
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SU914895583A RU2091374C1 (ru) | 1990-06-01 | 1991-05-31 | Способ получения замещенных 5-арил-пиримидинов |
Country Status (25)
| Country | Link |
|---|---|
| EP (2) | EP0679645A1 (enExample) |
| JP (1) | JPH06340634A (enExample) |
| KR (1) | KR920000733A (enExample) |
| AT (1) | ATE141263T1 (enExample) |
| AU (2) | AU652753B2 (enExample) |
| CA (1) | CA2043640A1 (enExample) |
| CZ (1) | CZ281070B6 (enExample) |
| DE (1) | DE69121317T2 (enExample) |
| DK (1) | DK0459819T3 (enExample) |
| ES (1) | ES2093078T3 (enExample) |
| FI (1) | FI912623A7 (enExample) |
| GB (1) | GB9012316D0 (enExample) |
| GR (1) | GR3021237T3 (enExample) |
| HU (2) | HUT58707A (enExample) |
| IE (1) | IE911861A1 (enExample) |
| IL (2) | IL113599A (enExample) |
| MY (2) | MY136248A (enExample) |
| NO (1) | NO180375C (enExample) |
| NZ (3) | NZ248501A (enExample) |
| PL (2) | PL170373B1 (enExample) |
| PT (1) | PT97827B (enExample) |
| RU (1) | RU2091374C1 (enExample) |
| SK (1) | SK278444B6 (enExample) |
| TW (1) | TW224460B (enExample) |
| ZA (1) | ZA914165B (enExample) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2208436C2 (ru) * | 1999-04-22 | 2003-07-20 | Еуроселтик С.А. | Способ изготовления фармацевтических лекарственных форм и их предшественников и фармацевтическая лекарственная форма |
| RU2217140C2 (ru) * | 1997-11-24 | 2003-11-27 | Байер Акциенгезелльшафт | Применение замещенных аминометил-хроманов для предотвращения дегенерации и для ускорения регенерации нервных клеток |
| RU2277911C2 (ru) * | 2000-02-25 | 2006-06-20 | Ф.Хоффманн-Ля Рош Аг | Модуляторы аденозиновых рецепторов |
Families Citing this family (28)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| FI895821A7 (fi) * | 1988-12-07 | 1990-06-08 | The Wellcome Foundation Ltd | Farmaseuttisesti aktivisia CNS-yhdisteitä |
| AU653203B2 (en) * | 1991-01-30 | 1994-09-22 | Wellcome Foundation Limited, The | Water-dispersible tablets |
| US5629016A (en) * | 1991-01-30 | 1997-05-13 | Glaxo Wellcome Inc. | Water-dispersible tablets |
| GB9215908D0 (en) * | 1992-07-27 | 1992-09-09 | Wellcome Found | Water dispersible tablets |
| JPH08504798A (ja) * | 1992-12-18 | 1996-05-21 | ザ ウエルカム ファウンデーション リミテッド | 酵素阻害薬としての，ピリミジン，ピリジン，プテリジノンおよびインダゾール誘導体 |
| GB9226377D0 (en) * | 1992-12-18 | 1993-02-10 | Babbedge Rachel C | Pharmaceutical compositions |
| US5698226A (en) * | 1993-07-13 | 1997-12-16 | Glaxo Wellcome Inc. | Water-dispersible tablets |
| GB9319341D0 (en) * | 1993-09-17 | 1993-11-03 | Wellcome Found | Novel process |
| FR2741879A1 (fr) * | 1995-12-05 | 1997-06-06 | Esteve Labor Dr | Derives de fluorophenyl-triazines et pyrimidines, leur preparation et leur application en tant que medicament |
| US6440965B1 (en) | 1997-10-15 | 2002-08-27 | Krenitsky Pharmaceuticals, Inc. | Substituted pyrimidine derivatives, their preparation and their use in the treatment of neurodegenerative or neurological disorders of the central nervous system |
| GB9726987D0 (en) | 1997-12-22 | 1998-02-18 | Glaxo Group Ltd | Compounds |
| US6583148B1 (en) | 1999-04-08 | 2003-06-24 | Krenitsky Pharmaceuticals, Inc. | Neurotrophic substituted pyrimidines |
| HU225917B1 (en) | 1999-09-16 | 2007-12-28 | Tanabe Seiyaku Co | Pyrimidine and pyrazine derivatives, pharmaceutical compositions containing them and their use |
| MXPA02010693A (es) | 2000-04-28 | 2003-03-10 | Tanabe Seiyaku Co | Compuestos ciclicos. |
| US7273868B2 (en) | 2000-04-28 | 2007-09-25 | Tanabe Seiyaku Co., Ltd. | Pyrazine derivatives |
| JP5154728B2 (ja) * | 2000-07-24 | 2013-02-27 | クレニツキー・ファーマシューティカルズ，インコーポレイテッド | 神経栄養活性を有する置換５−アルキニルピリミジン |
| JP4166991B2 (ja) | 2001-02-26 | 2008-10-15 | 田辺三菱製薬株式会社 | ピリドピリミジンまたはナフチリジン誘導体 |
| CN1628109A (zh) * | 2002-02-05 | 2005-06-15 | 诺沃挪第克公司 | 新颖的芳基－与杂芳基－哌嗪 |
| TW200637556A (en) * | 2005-01-31 | 2006-11-01 | Basf Ag | Substituted 5-phenyl pyrimidines I in therapy |
| MX2007015675A (es) | 2005-07-04 | 2008-02-20 | Novo Nordisk As | Antagonistas del receptor de histamina h3. |
| CA2653062A1 (en) | 2006-05-23 | 2007-11-29 | Transtech Pharma, Inc. | 6- (4-cyclopropylpiperazin-1-yl) -2 ' -methyl- [3, 4 ' ] -bipyridine and its use as a medicament |
| KR20090040259A (ko) | 2006-05-29 | 2009-04-23 | 하이 포인트 파마슈티칼스, 엘엘씨 | 3-(1,3-벤조디옥솔-5-일)-6-(4-시클로프로필피페라진-1-일)-피리다진, 그것의 염과 용매화합물 및 그것의 히스타민 ｈ3 수용체 안타고니스트로서의 용도 |
| EP2014656A3 (en) | 2007-06-11 | 2011-08-24 | High Point Pharmaceuticals, LLC | New heteocyclic h3 antagonists |
| LT2718270T (lt) * | 2011-06-10 | 2022-08-10 | Merck Patent Gmbh | Pirimidino ir piridino junginių, turinčių btk inhibitorinį aktyvumą, kompozicijos ir gamybos būdai |
| US10093646B2 (en) | 2014-01-17 | 2018-10-09 | Novartis Ag | 1-pyridazin-/triazin-3-yl-piper(-azine)/idine/pyrolidine derivatives and compositions thereof for inhibiting the activity of SHP2 |
| JO3517B1 (ar) | 2014-01-17 | 2020-07-05 | Novartis Ag | ان-ازاسبيرو الكان حلقي كبديل مركبات اريل-ان مغايرة وتركيبات لتثبيط نشاط shp2 |
| CN109415360B (zh) | 2016-06-14 | 2021-11-02 | 诺华股份有限公司 | 用于抑制shp2活性的化合物和组合物 |
| US20190343836A1 (en) | 2017-01-10 | 2019-11-14 | Novartis Ag | Pharmaceutical combination comprising an alk inhibitor and a shp2 inhibitor |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| BE518622A (enExample) * | ||||
| FI895821A7 (fi) * | 1988-12-07 | 1990-06-08 | The Wellcome Foundation Ltd | Farmaseuttisesti aktivisia CNS-yhdisteitä |
| US5136080A (en) * | 1989-12-04 | 1992-08-04 | Burroughs Wellcome Co. | Nitrile compounds |
-
1990
- 1990-06-01 GB GB909012316A patent/GB9012316D0/en active Pending
-
1991
- 1991-05-30 ZA ZA914165A patent/ZA914165B/xx unknown
- 1991-05-31 EP EP95111314A patent/EP0679645A1/en not_active Withdrawn
- 1991-05-31 IL IL113599A patent/IL113599A/xx not_active IP Right Cessation
- 1991-05-31 PT PT97827A patent/PT97827B/pt not_active IP Right Cessation
- 1991-05-31 IL IL9833091A patent/IL98330A/en active IP Right Grant
- 1991-05-31 NZ NZ248501A patent/NZ248501A/en unknown
- 1991-05-31 PL PL91305331A patent/PL170373B1/pl unknown
- 1991-05-31 MY MYPI95001459A patent/MY136248A/en unknown
- 1991-05-31 MY MYPI91000962A patent/MY109958A/en unknown
- 1991-05-31 RU SU914895583A patent/RU2091374C1/ru active
- 1991-05-31 CZ CS911643A patent/CZ281070B6/cs unknown
- 1991-05-31 JP JP3235334A patent/JPH06340634A/ja active Pending
- 1991-05-31 DE DE69121317T patent/DE69121317T2/de not_active Expired - Fee Related
- 1991-05-31 HU HU911826A patent/HUT58707A/hu unknown
- 1991-05-31 ES ES91304935T patent/ES2093078T3/es not_active Expired - Lifetime
- 1991-05-31 PL PL91290496A patent/PL166656B1/pl unknown
- 1991-05-31 EP EP91304935A patent/EP0459819B1/en not_active Expired - Lifetime
- 1991-05-31 DK DK91304935.9T patent/DK0459819T3/da active
- 1991-05-31 NO NO912100A patent/NO180375C/no unknown
- 1991-05-31 TW TW080104285A patent/TW224460B/zh active
- 1991-05-31 NZ NZ272001A patent/NZ272001A/en unknown
- 1991-05-31 AU AU78097/91A patent/AU652753B2/en not_active Ceased
- 1991-05-31 IE IE186191A patent/IE911861A1/en unknown
- 1991-05-31 AT AT91304935T patent/ATE141263T1/de not_active IP Right Cessation
- 1991-05-31 SK SK1643-91A patent/SK278444B6/sk unknown
- 1991-05-31 KR KR1019910009010A patent/KR920000733A/ko not_active Ceased
- 1991-05-31 CA CA002043640A patent/CA2043640A1/en not_active Abandoned
- 1991-05-31 NZ NZ238360A patent/NZ238360A/en unknown
- 1991-05-31 FI FI912623A patent/FI912623A7/fi not_active Application Discontinuation
-
1994
- 1994-07-13 AU AU67455/94A patent/AU680252B2/en not_active Expired - Fee Related
-
1995
- 1995-06-30 HU HU95P/P00669P patent/HU211649A9/hu unknown
-
1996
- 1996-10-03 GR GR960402585T patent/GR3021237T3/el unknown
Non-Patent Citations (1)
| Title |
|---|
| ЕР, патент, 0372934, кл. A 61 K 31/585, 1990. * |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| RU2217140C2 (ru) * | 1997-11-24 | 2003-11-27 | Байер Акциенгезелльшафт | Применение замещенных аминометил-хроманов для предотвращения дегенерации и для ускорения регенерации нервных клеток |
| RU2208436C2 (ru) * | 1999-04-22 | 2003-07-20 | Еуроселтик С.А. | Способ изготовления фармацевтических лекарственных форм и их предшественников и фармацевтическая лекарственная форма |
| RU2277911C2 (ru) * | 2000-02-25 | 2006-06-20 | Ф.Хоффманн-Ля Рош Аг | Модуляторы аденозиновых рецепторов |
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