SK284108B6 - 2,3-Disubstituované 4(3H)-chinazolinóny, ich použitie a farmaceutické kompozície s ich obsahom - Google Patents
2,3-Disubstituované 4(3H)-chinazolinóny, ich použitie a farmaceutické kompozície s ich obsahom Download PDFInfo
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- SK284108B6 SK284108B6 SK1520-98A SK152098A SK284108B6 SK 284108 B6 SK284108 B6 SK 284108B6 SK 152098 A SK152098 A SK 152098A SK 284108 B6 SK284108 B6 SK 284108B6
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- Prior art keywords
- alkyl
- carbon atoms
- fluoro
- moiety
- hydrogen
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- -1 2,3-disubstituted-4(3H)-quinazolinones Chemical class 0.000 title claims abstract description 81
- 150000003839 salts Chemical class 0.000 claims abstract description 54
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 7
- 125000000217 alkyl group Chemical group 0.000 claims description 148
- 125000004432 carbon atom Chemical group C* 0.000 claims description 132
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 64
- 229910052739 hydrogen Inorganic materials 0.000 claims description 61
- 239000001257 hydrogen Substances 0.000 claims description 50
- 239000000460 chlorine Substances 0.000 claims description 39
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 39
- 229910052757 nitrogen Inorganic materials 0.000 claims description 35
- 229910052736 halogen Inorganic materials 0.000 claims description 30
- 150000002367 halogens Chemical class 0.000 claims description 29
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 27
- 229910052799 carbon Inorganic materials 0.000 claims description 26
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 23
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- 229910052717 sulfur Inorganic materials 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 18
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 17
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- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
- 125000005843 halogen group Chemical group 0.000 claims description 14
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- CIHUEZBCQHMFRJ-UHFFFAOYSA-N 3-(2-bromophenyl)-2-[2-[6-(diethylaminomethyl)pyridin-2-yl]ethenyl]-6-fluoroquinazolin-4-one Chemical compound CCN(CC)CC1=CC=CC(C=CC=2N(C(=O)C3=CC(F)=CC=C3N=2)C=2C(=CC=CC=2)Br)=N1 CIHUEZBCQHMFRJ-UHFFFAOYSA-N 0.000 claims description 2
- VFGHAJFBOFUWGA-UHFFFAOYSA-N 3-(2-chlorophenyl)-2-[2-[5-(diethylaminomethyl)-2-fluorophenyl]ethenyl]-6-fluoroquinazolin-4-one Chemical compound CCN(CC)CC1=CC=C(F)C(C=CC=2N(C(=O)C3=CC(F)=CC=C3N=2)C=2C(=CC=CC=2)Cl)=C1 VFGHAJFBOFUWGA-UHFFFAOYSA-N 0.000 claims description 2
- HYHNPUGUPISSQO-UHFFFAOYSA-N 3-(2-chlorophenyl)-2-[2-[6-(diethylaminomethyl)pyridin-2-yl]ethenyl]-6-fluoroquinazolin-4-one Chemical compound CCN(CC)CC1=CC=CC(C=CC=2N(C(=O)C3=CC(F)=CC=C3N=2)C=2C(=CC=CC=2)Cl)=N1 HYHNPUGUPISSQO-UHFFFAOYSA-N 0.000 claims description 2
- CMMNTRYILRVWOP-UHFFFAOYSA-N 3-(2-chlorophenyl)-6-fluoro-2-[2-(4-methylpyrimidin-2-yl)ethenyl]quinazolin-4-one Chemical compound CC1=CC=NC(C=CC=2N(C(=O)C3=CC(F)=CC=C3N=2)C=2C(=CC=CC=2)Cl)=N1 CMMNTRYILRVWOP-UHFFFAOYSA-N 0.000 claims description 2
- WHDYQMOSUONVHJ-UHFFFAOYSA-N 3-(2-chlorophenyl)-6-fluoro-2-[2-[6-(methoxymethyl)pyridin-2-yl]ethenyl]quinazolin-4-one Chemical compound COCC1=CC=CC(C=CC=2N(C(=O)C3=CC(F)=CC=C3N=2)C=2C(=CC=CC=2)Cl)=N1 WHDYQMOSUONVHJ-UHFFFAOYSA-N 0.000 claims description 2
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Classifications
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- 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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- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
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- 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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- C07D239/86—Quinazolines; Hydrogenated quinazolines with hetero atoms directly attached in position 4
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- 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
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- C07D401/06—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 carbon chain containing only aliphatic carbon atoms
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- 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
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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
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- C07D403/06—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 carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms 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
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
- C07D417/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
- C07D417/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing three or more hetero rings
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- 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
- C07D491/10—Spiro-condensed systems
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- Chemical & Material Sciences (AREA)
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- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Neurosurgery (AREA)
- Neurology (AREA)
- Pain & Pain Management (AREA)
- Heart & Thoracic Surgery (AREA)
- Hospice & Palliative Care (AREA)
- Rheumatology (AREA)
- Cardiology (AREA)
- Psychiatry (AREA)
- Psychology (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Paints Or Removers (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US1773896P | 1996-05-15 | 1996-05-15 | |
PCT/IB1997/000134 WO1997043276A1 (en) | 1996-05-15 | 1997-02-17 | Novel 2,3 disubstituted-4(3h)-quinazolinones |
Publications (2)
Publication Number | Publication Date |
---|---|
SK152098A3 SK152098A3 (en) | 2000-05-16 |
SK284108B6 true SK284108B6 (sk) | 2004-09-08 |
Family
ID=21784266
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
SK1520-98A SK284108B6 (sk) | 1996-05-15 | 1997-02-17 | 2,3-Disubstituované 4(3H)-chinazolinóny, ich použitie a farmaceutické kompozície s ich obsahom |
Country Status (38)
Country | Link |
---|---|
US (1) | US6303615B1 (cs) |
EP (1) | EP0901487B9 (cs) |
JP (1) | JP3241388B2 (cs) |
KR (1) | KR100375155B1 (cs) |
CN (2) | CN1103772C (cs) |
AP (1) | AP1148A (cs) |
AR (1) | AR007118A1 (cs) |
AT (1) | ATE242232T1 (cs) |
AU (1) | AU730503B2 (cs) |
BG (1) | BG102999A (cs) |
BR (1) | BR9709085A (cs) |
CA (1) | CA2252907C (cs) |
CZ (1) | CZ295565B6 (cs) |
DE (1) | DE69722613T2 (cs) |
DK (1) | DK0901487T3 (cs) |
DZ (1) | DZ2237A1 (cs) |
EA (1) | EA002905B1 (cs) |
ES (1) | ES2198546T3 (cs) |
GT (1) | GT199700049A (cs) |
HN (1) | HN1997000052A (cs) |
HR (1) | HRP970261B1 (cs) |
HU (1) | HUP9902148A3 (cs) |
ID (1) | ID17149A (cs) |
IL (1) | IL126589A (cs) |
IS (1) | IS4881A (cs) |
MA (1) | MA26430A1 (cs) |
NO (1) | NO985293L (cs) |
OA (1) | OA10918A (cs) |
PL (1) | PL330042A1 (cs) |
PT (1) | PT901487E (cs) |
SI (1) | SI0901487T1 (cs) |
SK (1) | SK284108B6 (cs) |
TN (1) | TNSN97087A1 (cs) |
TR (1) | TR199802296T2 (cs) |
TW (1) | TW539675B (cs) |
WO (1) | WO1997043276A1 (cs) |
YU (1) | YU19197A (cs) |
ZA (1) | ZA974156B (cs) |
Families Citing this family (43)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
BR9807807A (pt) * | 1997-02-28 | 2000-02-22 | Pfizer Prod Inc | AtropisÈmeros de 3-heteroaril-4(3h)-quinazolinonas para o tratamento de condições neurodegenerativas e relacionadas com trauma do sistema nervoso central (snc) |
ATE267817T1 (de) * | 1997-02-28 | 2004-06-15 | Pfizer Prod Inc | Atropisomere von 3-aryl-4(3h)-chinazolinonen und ihre verwendung als ampa-rezeptor |
US6060479A (en) * | 1997-06-09 | 2000-05-09 | Pfizer Inc | Quinazoline-4-one AMPA antagonists |
IL125950A0 (en) * | 1997-09-05 | 1999-04-11 | Pfizer Prod Inc | Methods of administering ampa receptor antagonists to treat dyskinesias associated with dopamine agonist therapy |
EP0900567A3 (en) * | 1997-09-05 | 2001-05-02 | Pfizer Products Inc. | Quinazoline-4-one AMPA antagonists for the treatment of dyskinesias associated with dopamine agonist therapy |
JPH11279158A (ja) * | 1998-02-09 | 1999-10-12 | Pfizer Prod Inc | キナゾリン―4―オン誘導体の製造方法 |
TWI258472B (en) | 1999-02-15 | 2006-07-21 | Eisai Co Ltd | Heterodiazinone derivatives |
US6890930B1 (en) * | 1999-09-28 | 2005-05-10 | 3-Dimensional Pharmaceuticals, Inc. | Quinazolinones |
US6545004B1 (en) | 1999-10-27 | 2003-04-08 | Cytokinetics, Inc. | Methods and compositions utilizing quinazolinones |
US7230000B1 (en) | 1999-10-27 | 2007-06-12 | Cytokinetics, Incorporated | Methods and compositions utilizing quinazolinones |
US20020061897A1 (en) | 2000-03-30 | 2002-05-23 | Elliott Richard L. | Neuropeptide Y antagonists |
US6667300B2 (en) | 2000-04-25 | 2003-12-23 | Icos Corporation | Inhibitors of human phosphatidylinositol 3-kinase delta |
KR100869271B1 (ko) | 2000-06-12 | 2008-11-18 | 에자이 알앤드디 매니지먼트 가부시키가이샤 | 1,2-디하이드로피리딘 화합물 및 그의 용도 |
WO2003043961A2 (en) * | 2001-11-19 | 2003-05-30 | Iconix Pharmaceuticals, Inc. | Modulators of rho c activity |
GB0129260D0 (en) | 2001-12-06 | 2002-01-23 | Eisai London Res Lab Ltd | Pharmaceutical compositions and their uses |
JP2005529076A (ja) | 2002-02-15 | 2005-09-29 | サイトキネティクス・インコーポレーテッド | キナゾリノンの合成 |
JP2005530785A (ja) | 2002-05-09 | 2005-10-13 | サイトキネティクス・インコーポレーテッド | 化合物、組成物、及び方法 |
NZ537076A (en) | 2002-05-09 | 2007-06-29 | Cytokinetics Inc | Pyrimidinone compounds, compositions and methods |
EP1513820A4 (en) | 2002-05-23 | 2006-09-13 | Cytokinetics Inc | COMPOUNDS, COMPOSITIONS AND METHODS |
WO2003106426A1 (en) | 2002-06-14 | 2003-12-24 | Cytokinetics, Inc. | Compounds, compositions, and methods |
US7211580B2 (en) | 2002-07-23 | 2007-05-01 | Cytokinetics, Incorporated | Compounds, compositions, and methods |
EP1558083A4 (en) | 2002-09-30 | 2008-04-16 | Cytokinetics Inc | COMPOUNDS, COMPOSITIONS AND METHODS |
US7439254B2 (en) | 2003-12-08 | 2008-10-21 | Cytokinetics, Inc. | Compounds, compositions, and methods |
RS55546B1 (sr) | 2004-05-13 | 2017-05-31 | Icos Corp | Hinazolinoni kao inhibitori humane fosfatidilonozitol 3-delta kinaze |
MY148809A (en) | 2004-07-06 | 2013-05-31 | Eisai R&D Man Co Ltd | Crystals of 1,2-dihydropyridine compound and their production process |
CN101355946B (zh) * | 2005-11-04 | 2013-05-08 | 海德拉生物科学公司 | 调节trpv3功能的化合物 |
CN101547922B (zh) | 2006-10-04 | 2012-06-20 | 辉瑞产品公司 | 作为钙受体拮抗剂的吡啶并[4,3-d]嘧啶-4(3H)-酮衍生物 |
WO2008140750A1 (en) * | 2007-05-10 | 2008-11-20 | Hydra Biosciences Inc. | Compounds for modulating trpv3 function |
RU2476432C2 (ru) * | 2007-09-26 | 2013-02-27 | Селджин Корпорейшн | 6-, 7- или 8-замещенные производные хиназолинона и композиции, включающие их, и способы их использования |
US8404696B2 (en) | 2008-01-30 | 2013-03-26 | Shin Poong Pharmaceutical Co., Ltd. | Quinazoline-2,4-dione derivative, and medical compositions for the prophylaxis and treatment of cranial nerve disease containing the same |
WO2010057048A1 (en) | 2008-11-13 | 2010-05-20 | Calistoga Pharmaceuticals Inc. | Therapies for hematologic malignancies |
US9492449B2 (en) | 2008-11-13 | 2016-11-15 | Gilead Calistoga Llc | Therapies for hematologic malignancies |
EP2411391A1 (en) | 2009-03-24 | 2012-02-01 | Gilead Calistoga LLC | Atropisomers of2-purinyl-3-tolyl-quinazolinone derivatives and methods of use |
AU2010239312A1 (en) | 2009-04-20 | 2011-11-10 | Gilead Calistoga Llc | Methods of treatment for solid tumors |
AU2010276160A1 (en) | 2009-07-21 | 2012-02-09 | Gilead Calistoga Llc | Treatment of liver disorders with PI3K inhibitors |
WO2013105985A1 (en) * | 2011-02-28 | 2013-07-18 | Philadelphia Health & Education Corporation | Small molecule inhibitors of rad51 recombinase and methods thereof |
US8865730B2 (en) | 2012-03-05 | 2014-10-21 | Gilead Calistoga Llc | Polymorphic forms of (S)-2-(1-(9H-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3H)-one |
PT3083630T (pt) | 2013-12-20 | 2019-11-15 | Gilead Calistoga Llc | Procedimentos para inibidores da fosfatidilinositol 3-quinase |
CA2934534A1 (en) | 2013-12-20 | 2015-06-25 | Gilead Calistoga Llc | Polymorphic forms of a hydrochloride salt of (s)-2-(1-(9h-purin-6-ylamino)propyl)-5-fluoro-3-phenylquinazolin-4(3h)-one |
JP6455995B2 (ja) | 2014-06-13 | 2019-01-23 | ギリアード サイエンシーズ, インコーポレイテッド | ホスファチジルイノシトール3−キナーゼ阻害剤 |
WO2020124090A1 (en) | 2018-12-14 | 2020-06-18 | Eisai R&D Management Co., Ltd. | Aqueous based pharmaceutical formulations of 1,2-dihydropyridine compounds |
CA3168103A1 (en) | 2020-01-29 | 2021-08-05 | Kamari Pharma Ltd. | Compounds and compositions for use in treating skin disorders |
CN113831335A (zh) * | 2020-06-24 | 2021-12-24 | 北京大学 | 吡啶[2,3-d]并嘧啶-4-(3H)-酮类化合物及其制备方法和应用 |
Family Cites Families (10)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE1195321B (de) * | 1962-03-16 | 1965-06-24 | Troponwerke Dinklage & Co | Verfahren zur Herstellung von substituierten Chinazolon-(4)-derivaten |
DE1670416A1 (de) * | 1966-12-30 | 1971-02-11 | Chem Fab Von Heyden Gmbh Muenc | Verfahren zur Herstellung von aminosubstituierten Chinazolinonderivaten |
US3748325A (en) | 1970-04-06 | 1973-07-24 | Karamchand Premchand Private | Process for the preparation of quinazolinone derivatives |
AU543928B2 (en) * | 1981-01-16 | 1985-05-09 | Masayuki Ishikawa | 4(311)-quinazolinone derivatives |
GB9022785D0 (en) | 1990-10-19 | 1990-12-05 | Merck Sharp & Dohme | Therapeutic agents |
WO1992013535A1 (en) * | 1991-02-06 | 1992-08-20 | Research Corporation Technologies, Inc. | Anticonvulsant substituted quinazolones |
US5284957A (en) | 1992-09-03 | 1994-02-08 | Eli Lilly And Company | Excitatory amino acid receptor antagonists |
DK0698024T3 (da) | 1993-05-06 | 1997-07-28 | Novo Nordisk As | 1,2,4 triazolo 4,3-a quinoxalinforbindelser, deres fremstilling og anvendelse |
GB9400680D0 (en) * | 1994-01-14 | 1994-03-09 | Sandoz Ltd | Improvements in or relating to organic compounds |
ATE267817T1 (de) | 1997-02-28 | 2004-06-15 | Pfizer Prod Inc | Atropisomere von 3-aryl-4(3h)-chinazolinonen und ihre verwendung als ampa-rezeptor |
-
1997
- 1997-02-17 EA EA199800923A patent/EA002905B1/ru not_active IP Right Cessation
- 1997-02-17 CA CA002252907A patent/CA2252907C/en not_active Expired - Fee Related
- 1997-02-17 EP EP97901749A patent/EP0901487B9/en not_active Expired - Lifetime
- 1997-02-17 US US09/180,732 patent/US6303615B1/en not_active Expired - Fee Related
- 1997-02-17 PT PT97901749T patent/PT901487E/pt unknown
- 1997-02-17 TR TR1998/02296T patent/TR199802296T2/xx unknown
- 1997-02-17 CN CN97194654A patent/CN1103772C/zh not_active Expired - Fee Related
- 1997-02-17 DK DK97901749T patent/DK0901487T3/da active
- 1997-02-17 DE DE69722613T patent/DE69722613T2/de not_active Expired - Fee Related
- 1997-02-17 SI SI9730555T patent/SI0901487T1/xx unknown
- 1997-02-17 SK SK1520-98A patent/SK284108B6/sk unknown
- 1997-02-17 JP JP54068297A patent/JP3241388B2/ja not_active Expired - Fee Related
- 1997-02-17 CZ CZ19983526A patent/CZ295565B6/cs not_active IP Right Cessation
- 1997-02-17 AT AT97901749T patent/ATE242232T1/de not_active IP Right Cessation
- 1997-02-17 BR BR9709085A patent/BR9709085A/pt not_active Application Discontinuation
- 1997-02-17 KR KR10-1998-0709205A patent/KR100375155B1/ko not_active Expired - Fee Related
- 1997-02-17 HU HU9902148A patent/HUP9902148A3/hu unknown
- 1997-02-17 WO PCT/IB1997/000134 patent/WO1997043276A1/en active IP Right Grant
- 1997-02-17 PL PL97330042A patent/PL330042A1/xx unknown
- 1997-02-17 AU AU15549/97A patent/AU730503B2/en not_active Ceased
- 1997-02-17 ES ES97901749T patent/ES2198546T3/es not_active Expired - Lifetime
- 1997-04-08 TW TW086104460A patent/TW539675B/zh active
- 1997-04-21 HN HN1997000052A patent/HN1997000052A/es unknown
- 1997-04-29 GT GT199700049A patent/GT199700049A/es unknown
- 1997-05-13 AR ARP970102001A patent/AR007118A1/es not_active Application Discontinuation
- 1997-05-14 YU YU19197A patent/YU19197A/sh unknown
- 1997-05-14 TN TNTNSN97087A patent/TNSN97087A1/fr unknown
- 1997-05-14 ZA ZA974156A patent/ZA974156B/xx unknown
- 1997-05-14 ID IDP971603A patent/ID17149A/id unknown
- 1997-05-14 DZ DZ970085A patent/DZ2237A1/fr active
- 1997-05-14 MA MA24613A patent/MA26430A1/fr unknown
- 1997-05-15 HR HR970261A patent/HRP970261B1/xx not_active IP Right Cessation
- 1997-05-15 AP APAP/P/1997/001003A patent/AP1148A/en active
- 1997-12-17 IL IL12658997A patent/IL126589A/xx not_active IP Right Cessation
-
1998
- 1998-10-27 IS IS4881A patent/IS4881A/is unknown
- 1998-11-06 OA OA9800216A patent/OA10918A/en unknown
- 1998-11-13 NO NO985293A patent/NO985293L/no unknown
- 1998-12-08 BG BG102999A patent/BG102999A/xx unknown
-
2002
- 2002-09-05 CN CN02131946A patent/CN1420114A/zh active Pending
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