NO310072B1 - Pyrimidinderivater som 5HT2C-reseptor antagonister - Google Patents
Pyrimidinderivater som 5HT2C-reseptor antagonister Download PDFInfo
- Publication number
- NO310072B1 NO310072B1 NO981477A NO981477A NO310072B1 NO 310072 B1 NO310072 B1 NO 310072B1 NO 981477 A NO981477 A NO 981477A NO 981477 A NO981477 A NO 981477A NO 310072 B1 NO310072 B1 NO 310072B1
- Authority
- NO
- Norway
- Prior art keywords
- formula
- compound
- methoxy
- dihydrobenzo
- quinazoline
- Prior art date
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Classifications
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- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/74—Quinazolines; Hydrogenated quinazolines with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, attached to ring carbon atoms of the hetero ring
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/70—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings condensed with carbocyclic rings or ring systems
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
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- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/80—Oxygen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
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- C07D239/72—Quinazolines; Hydrogenated quinazolines
- C07D239/78—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 2
- C07D239/84—Nitrogen atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
- C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
- C07D405/12—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
- C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
- C07D491/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
Landscapes
- Organic Chemistry (AREA)
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Psychiatry (AREA)
- Pain & Pain Management (AREA)
- Addiction (AREA)
- Anesthesiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (2)
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| US473395P | 1995-10-02 | 1995-10-02 | |
| PCT/EP1996/004099 WO1997012880A1 (en) | 1995-10-02 | 1996-09-19 | Pyrimidine derivatives as 5ht2c-receptor antagonists |
Publications (3)
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| NO981477D0 NO981477D0 (no) | 1998-04-01 |
| NO981477L NO981477L (no) | 1998-06-02 |
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| NO981477A NO310072B1 (no) | 1995-10-02 | 1998-04-01 | Pyrimidinderivater som 5HT2C-reseptor antagonister |
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| NO (1) | NO310072B1 (cs) |
| NZ (1) | NZ319158A (cs) |
| PL (1) | PL326083A1 (cs) |
| PT (1) | PT856001E (cs) |
| WO (1) | WO1997012880A1 (cs) |
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| GB9222253D0 (en) * | 1992-10-23 | 1992-12-09 | Celltech Ltd | Chemical compounds |
| GB9304920D0 (en) * | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| GB9304919D0 (en) * | 1993-03-10 | 1993-04-28 | Celltech Ltd | Chemical compounds |
| US6245774B1 (en) | 1994-06-21 | 2001-06-12 | Celltech Therapeutics Limited | Tri-substituted phenyl or pyridine derivatives |
| US5786354A (en) * | 1994-06-21 | 1998-07-28 | Celltech Therapeutics, Limited | Tri-substituted phenyl derivatives and processes for their preparation |
| GB9412573D0 (en) | 1994-06-22 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| GB9412571D0 (en) | 1994-06-22 | 1994-08-10 | Celltech Ltd | Chemical compounds |
| CA2218503C (en) * | 1995-04-20 | 2001-07-24 | Pfizer Inc. | Arylsulfonyl hydroxamic acid derivatives |
| GB9523675D0 (en) * | 1995-11-20 | 1996-01-24 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9619284D0 (en) * | 1996-09-16 | 1996-10-30 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9622363D0 (en) * | 1996-10-28 | 1997-01-08 | Celltech Therapeutics Ltd | Chemical compounds |
| WO1998028281A1 (en) | 1996-12-23 | 1998-07-02 | Celltech Therapeutics Limited | Fused polycyclic 2-aminopyrimidine derivatives, their preparation and their use as protein tyrosine kinase inhibitors |
| GB9705361D0 (en) | 1997-03-14 | 1997-04-30 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9713087D0 (en) * | 1997-06-20 | 1997-08-27 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9914258D0 (en) * | 1999-06-18 | 1999-08-18 | Celltech Therapeutics Ltd | Chemical compounds |
| GB9924862D0 (en) * | 1999-10-20 | 1999-12-22 | Celltech Therapeutics Ltd | Chemical compounds |
| US20030176454A1 (en) * | 2000-05-15 | 2003-09-18 | Akira Yamada | N-coating heterocyclic compounds |
| BR0209774A (pt) * | 2001-05-29 | 2004-06-01 | Schering Ag | Pirimidinas inibidoras de cdk, sua preparação e aplicação como medicamento |
| RS20060097A (sr) | 2002-12-20 | 2008-11-28 | Pfizer Products Inc., | Derivati pirimidina za lečenje nekontrolisanog rasta ćelija |
| US7109337B2 (en) | 2002-12-20 | 2006-09-19 | Pfizer Inc | Pyrimidine derivatives for the treatment of abnormal cell growth |
| UA80767C2 (en) * | 2002-12-20 | 2007-10-25 | Pfizer Prod Inc | Pyrimidine derivatives for the treatment of abnormal cell growth |
| CN1897950A (zh) | 2003-10-14 | 2007-01-17 | 惠氏公司 | 稠合芳基和杂芳基衍生物及其使用方法 |
| CA2566477A1 (en) | 2004-05-14 | 2005-11-24 | Pfizer Products Inc. | Pyrimidine derivatives for the treatment of abnormal cell growth |
| BRPI0510963A (pt) | 2004-05-14 | 2007-11-20 | Pfizer Prod Inc | derivados pirimidina para o tratamento do crescimento anormal de células |
| JP2007537230A (ja) | 2004-05-14 | 2007-12-20 | ファイザー・プロダクツ・インク | 異常細胞増殖の処置用のピリミジン誘導体 |
| US20060205945A1 (en) * | 2004-05-14 | 2006-09-14 | Pfizer Inc | Pyrimidine derivatives for the treatment of abnormal cell growth |
| CN101137381B (zh) * | 2005-03-15 | 2011-07-27 | 弗·哈夫曼-拉罗切有限公司 | 2-苯胺基-3,4-二氢-喹唑啉作为5ht5a受体拮抗剂的制药用途 |
| WO2009081222A1 (en) | 2007-12-21 | 2009-07-02 | Glenmark Pharmaceuticals, S.A. | Substituted tricyclic pyridine or pyrimidine vanilloid receptor ligands |
| MY162502A (en) * | 2008-11-20 | 2017-06-15 | Merck Sharp & Dohme | Aryl methyl benzoquinazolinone m1 receptor positive allosteric modulators |
| BRPI0923786C8 (pt) * | 2008-12-30 | 2021-05-25 | Arqule Inc | compostos 5,6-dihidro-6-fenilbenzo(f) isoquinolina-2- amina substituidos e composições farmacêuticas compreendendo ditos compostos |
| EP2512245B1 (en) * | 2009-12-14 | 2014-07-23 | Merck Sharp & Dohme Corp. | Pyridoquinazolinone m1 receptor positive allosteric modulators |
| WO2011084371A1 (en) * | 2009-12-21 | 2011-07-14 | Merck Sharp & Dohme Corp. | Aminobenzoquinazolinone m1 receptor positive allosteric modulators |
| TWI402264B (zh) * | 2010-05-12 | 2013-07-21 | Merck Sharp & Dohme | 芳基甲基苯并喹唑啉酮ｍ１受體之正向異位性調節劑 |
| US8735386B2 (en) * | 2010-07-23 | 2014-05-27 | Boehringer Ingelheim International Gmbh | Aminopyrazoloquinazolines |
| CA2858882C (en) | 2011-12-13 | 2021-02-02 | Trustees Of Dartmouth College | Autoimmune disorder treatment using rxr agonists |
| CN103214489B (zh) * | 2013-02-25 | 2016-10-26 | 中国人民解放军第二军医大学 | 一类具有抗肿瘤活性的多靶点激酶抑制剂及其制备方法 |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3177216A (en) | 1961-12-28 | 1965-04-06 | Searle & Co | 4-trifluoromethyl-2-thio-5h-alka[d]-pyrimidines and congeners |
| US3257400A (en) * | 1964-06-10 | 1966-06-21 | Searle & Co | 2-amino-5, 6-dihydrobenzo[h]quinazolin-4(3h)-one and congeners |
| US3925384A (en) * | 1974-10-21 | 1975-12-09 | Squibb & Sons Inc | 2-Amino-4,5-dihydro-4-arylindeno pyrimidines |
| IL103502A0 (en) * | 1991-10-24 | 1993-03-15 | Merck Sharp & Dohme | Benzodiazepine derivatives,their preparation and pharmaceutical compositions containing them |
-
1996
- 1996-09-19 CZ CZ98989A patent/CZ98998A3/cs unknown
- 1996-09-19 EA EA199800340A patent/EA001311B1/ru not_active IP Right Cessation
- 1996-09-19 NZ NZ319158A patent/NZ319158A/en unknown
- 1996-09-19 MX MX9802383A patent/MX9802383A/es not_active IP Right Cessation
- 1996-09-19 PL PL96326083A patent/PL326083A1/xx unknown
- 1996-09-19 EP EP96932569A patent/EP0856001B1/en not_active Expired - Lifetime
- 1996-09-19 BR BR9610823A patent/BR9610823A/pt not_active IP Right Cessation
- 1996-09-19 AT AT96932569T patent/ATE222892T1/de not_active IP Right Cessation
- 1996-09-19 ES ES96932569T patent/ES2180798T3/es not_active Expired - Lifetime
- 1996-09-19 CN CN96197385A patent/CN1118460C/zh not_active Expired - Fee Related
- 1996-09-19 PT PT96932569T patent/PT856001E/pt unknown
- 1996-09-19 DK DK96932569T patent/DK0856001T3/da active
- 1996-09-19 HU HU9802323A patent/HUP9802323A3/hu unknown
- 1996-09-19 JP JP9513926A patent/JP3071830B2/ja not_active Expired - Fee Related
- 1996-09-19 IL IL12358196A patent/IL123581A/en not_active IP Right Cessation
- 1996-09-19 CA CA002233003A patent/CA2233003A1/en not_active Abandoned
- 1996-09-19 AU AU71311/96A patent/AU700637B2/en not_active Ceased
- 1996-09-19 WO PCT/EP1996/004099 patent/WO1997012880A1/en not_active Ceased
- 1996-09-19 DE DE69623306T patent/DE69623306T2/de not_active Expired - Fee Related
- 1996-09-19 KR KR1019980702391A patent/KR100258052B1/ko not_active Expired - Fee Related
- 1996-09-24 US US08/719,062 patent/US5753663A/en not_active Expired - Fee Related
- 1996-10-01 AR ARP960104557A patent/AR004516A1/es unknown
-
1998
- 1998-04-01 NO NO981477A patent/NO310072B1/no unknown
Also Published As
| Publication number | Publication date |
|---|---|
| CZ98998A3 (cs) | 1998-10-14 |
| NO981477D0 (no) | 1998-04-01 |
| EP0856001B1 (en) | 2002-08-28 |
| AU700637B2 (en) | 1999-01-07 |
| PT856001E (pt) | 2003-01-31 |
| NO981477L (no) | 1998-06-02 |
| HUP9802323A3 (en) | 1999-08-30 |
| JPH10512288A (ja) | 1998-11-24 |
| EA001311B1 (ru) | 2001-02-26 |
| DE69623306D1 (de) | 2002-10-02 |
| US5753663A (en) | 1998-05-19 |
| MX9802383A (es) | 1998-08-30 |
| IL123581A0 (en) | 1998-10-30 |
| ES2180798T3 (es) | 2003-02-16 |
| CA2233003A1 (en) | 1997-04-10 |
| KR19990063918A (ko) | 1999-07-26 |
| DE69623306T2 (de) | 2003-04-17 |
| IL123581A (en) | 2001-09-13 |
| NZ319158A (en) | 1999-10-28 |
| DK0856001T3 (da) | 2002-12-30 |
| KR100258052B1 (ko) | 2000-08-01 |
| ATE222892T1 (de) | 2002-09-15 |
| AR004516A1 (es) | 1998-12-16 |
| BR9610823A (pt) | 1999-07-13 |
| HUP9802323A2 (hu) | 1999-03-29 |
| WO1997012880A1 (en) | 1997-04-10 |
| JP3071830B2 (ja) | 2000-07-31 |
| EA199800340A1 (ru) | 1998-10-29 |
| EP0856001A1 (en) | 1998-08-05 |
| CN1198743A (zh) | 1998-11-11 |
| PL326083A1 (en) | 1998-08-17 |
| AU7131196A (en) | 1997-04-28 |
| CN1118460C (zh) | 2003-08-20 |
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