CN1315822C - 具有vegf抑制活性的喹啉衍生物 - Google Patents
具有vegf抑制活性的喹啉衍生物 Download PDFInfo
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- CN1315822C CN1315822C CNB018139000A CN01813900A CN1315822C CN 1315822 C CN1315822 C CN 1315822C CN B018139000 A CNB018139000 A CN B018139000A CN 01813900 A CN01813900 A CN 01813900A CN 1315822 C CN1315822 C CN 1315822C
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- Prior art keywords
- alkyl
- group
- ethyl
- base
- methyl
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- 125000002943 quinolinyl group Chemical class N1=C(C=CC2=CC=CC=C12)* 0.000 title claims description 19
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 title abstract description 17
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 title abstract description 17
- 230000002401 inhibitory effect Effects 0.000 title description 2
- 229940027991 antiseptic and disinfectant quinoline derivative Drugs 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims abstract description 180
- 150000003839 salts Chemical class 0.000 claims abstract description 108
- 239000001257 hydrogen Substances 0.000 claims abstract description 94
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 94
- 238000000034 method Methods 0.000 claims abstract description 93
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 80
- 230000000694 effects Effects 0.000 claims abstract description 29
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 26
- 238000002360 preparation method Methods 0.000 claims abstract description 25
- 230000008728 vascular permeability Effects 0.000 claims abstract description 20
- 239000003814 drug Substances 0.000 claims abstract description 19
- 241001465754 Metazoa Species 0.000 claims abstract description 18
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 5
- -1 pyrrolidyl Chemical group 0.000 claims description 1006
- 239000002585 base Substances 0.000 claims description 506
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 294
- 229910052760 oxygen Inorganic materials 0.000 claims description 156
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 126
- 239000001301 oxygen Substances 0.000 claims description 122
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 117
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 110
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 96
- 229910052736 halogen Inorganic materials 0.000 claims description 82
- 150000002367 halogens Chemical class 0.000 claims description 82
- 125000000217 alkyl group Chemical group 0.000 claims description 79
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 60
- 238000006243 chemical reaction Methods 0.000 claims description 55
- 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 53
- 125000005936 piperidyl group Chemical group 0.000 claims description 49
- 125000002393 azetidinyl group Chemical group 0.000 claims description 47
- RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 46
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 42
- 125000004193 piperazinyl group Chemical group 0.000 claims description 36
- BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 claims description 36
- 229910052799 carbon Inorganic materials 0.000 claims description 34
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 34
- 229910052717 sulfur Inorganic materials 0.000 claims description 34
- 125000004122 cyclic group Chemical group 0.000 claims description 32
- 125000000623 heterocyclic group Chemical group 0.000 claims description 31
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 29
- 150000001721 carbon Chemical group 0.000 claims description 24
- 239000003513 alkali Substances 0.000 claims description 20
- PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 17
- 230000009467 reduction Effects 0.000 claims description 16
- 125000002853 C1-C4 hydroxyalkyl group Chemical group 0.000 claims description 15
- 239000004037 angiogenesis inhibitor Substances 0.000 claims description 14
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 claims description 13
- 229940121369 angiogenesis inhibitor Drugs 0.000 claims description 13
- 125000001424 substituent group Chemical group 0.000 claims description 12
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- 125000001041 indolyl group Chemical group 0.000 claims description 9
- 125000002861 (C1-C4) alkanoyl group Chemical group 0.000 claims description 5
- JTSFIVQMXUDGAB-UHFFFAOYSA-N 4-thiomorpholin-4-ylmorpholine Chemical compound C1COCCN1N1CCSCC1 JTSFIVQMXUDGAB-UHFFFAOYSA-N 0.000 claims description 5
- 206010028980 Neoplasm Diseases 0.000 abstract description 20
- 238000011282 treatment Methods 0.000 abstract description 19
- 125000001153 fluoro group Chemical group F* 0.000 abstract description 9
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- 238000004519 manufacturing process Methods 0.000 abstract description 5
- 201000010099 disease Diseases 0.000 abstract description 4
- 206010039073 rheumatoid arthritis Diseases 0.000 abstract description 4
- 239000004480 active ingredient Substances 0.000 abstract description 3
- 230000001772 anti-angiogenic effect Effects 0.000 abstract 1
- 230000001603 reducing effect Effects 0.000 abstract 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 294
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 186
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 122
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 102
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 76
- 239000000203 mixture Substances 0.000 description 73
- 238000005160 1H NMR spectroscopy Methods 0.000 description 72
- 238000001228 spectrum Methods 0.000 description 72
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 68
- 150000002431 hydrogen Chemical class 0.000 description 66
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 63
- 239000000243 solution Substances 0.000 description 50
- 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 46
- 229910052731 fluorine Inorganic materials 0.000 description 42
- 239000011737 fluorine Substances 0.000 description 42
- 239000002994 raw material Substances 0.000 description 37
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 36
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 35
- 238000005406 washing Methods 0.000 description 34
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 32
- 125000004397 aminosulfonyl group Chemical group NS(=O)(=O)* 0.000 description 32
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 30
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- 238000004440 column chromatography Methods 0.000 description 28
- 238000003756 stirring Methods 0.000 description 27
- 238000001704 evaporation Methods 0.000 description 26
- 230000008020 evaporation Effects 0.000 description 26
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 24
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 description 24
- 150000002148 esters Chemical class 0.000 description 22
- 239000012044 organic layer Substances 0.000 description 22
- 125000000304 alkynyl group Chemical group 0.000 description 21
- 150000001408 amides Chemical class 0.000 description 21
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 21
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 20
- 239000000460 chlorine Substances 0.000 description 20
- 229910052801 chlorine Inorganic materials 0.000 description 20
- 210000004027 cell Anatomy 0.000 description 16
- 239000007787 solid Substances 0.000 description 16
- 239000000725 suspension Substances 0.000 description 16
- UMWRMOYYUHIPDT-UHFFFAOYSA-N 4-fluoro-2-methyl-1h-indol-5-ol Chemical class OC1=CC=C2NC(C)=CC2=C1F UMWRMOYYUHIPDT-UHFFFAOYSA-N 0.000 description 15
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 15
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 15
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 15
- 229910052794 bromium Inorganic materials 0.000 description 15
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 14
- 238000001816 cooling Methods 0.000 description 14
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 14
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 14
- 239000000047 product Substances 0.000 description 14
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- 229940002612 prodrug Drugs 0.000 description 13
- 239000000651 prodrug Substances 0.000 description 13
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
- 239000000706 filtrate Substances 0.000 description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
- BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 description 11
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 11
- 125000003545 alkoxy group Chemical group 0.000 description 11
- 230000002349 favourable effect Effects 0.000 description 11
- 238000010438 heat treatment Methods 0.000 description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 10
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 10
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 10
- 125000003342 alkenyl group Chemical group 0.000 description 10
- 238000010790 dilution Methods 0.000 description 10
- 239000012895 dilution Substances 0.000 description 10
- 125000003453 indazolyl group Chemical group N1N=C(C2=C1C=CC=C2)* 0.000 description 10
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 10
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 10
- 238000001291 vacuum drying Methods 0.000 description 10
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 9
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 9
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
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- 102000004190 Enzymes Human genes 0.000 description 8
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- UCKMPCXJQFINFW-UHFFFAOYSA-N Sulphide Chemical compound [S-2] UCKMPCXJQFINFW-UHFFFAOYSA-N 0.000 description 8
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- LEQAOMBKQFMDFZ-UHFFFAOYSA-N alpha-ketodiacetal Natural products O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 description 8
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- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
- CNFDGXZLMLFIJV-UHFFFAOYSA-L manganese(II) chloride tetrahydrate Chemical compound O.O.O.O.[Cl-].[Cl-].[Mn+2] CNFDGXZLMLFIJV-UHFFFAOYSA-L 0.000 description 8
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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
- C07D401/14—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 three or more hetero rings
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Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP00402254 | 2000-08-09 | ||
| EP00402254.7 | 2000-08-09 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1446212A CN1446212A (zh) | 2003-10-01 |
| CN1315822C true CN1315822C (zh) | 2007-05-16 |
Family
ID=8173805
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB018139000A Expired - Fee Related CN1315822C (zh) | 2000-08-09 | 2001-08-08 | 具有vegf抑制活性的喹啉衍生物 |
Country Status (14)
| Country | Link |
|---|---|
| US (2) | US7371765B2 (enExample) |
| EP (1) | EP1313726A1 (enExample) |
| JP (1) | JP2004505964A (enExample) |
| KR (1) | KR20030036686A (enExample) |
| CN (1) | CN1315822C (enExample) |
| AU (2) | AU2001276536B2 (enExample) |
| BR (1) | BR0113056A (enExample) |
| CA (1) | CA2415469A1 (enExample) |
| IL (2) | IL153947A0 (enExample) |
| MX (1) | MXPA03000252A (enExample) |
| NO (1) | NO326315B1 (enExample) |
| NZ (1) | NZ523358A (enExample) |
| WO (1) | WO2002012226A1 (enExample) |
| ZA (1) | ZA200300217B (enExample) |
Families Citing this family (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| PL199802B1 (pl) | 1999-02-10 | 2008-10-31 | Astrazeneca Ab | Pochodne chinazoliny, sposoby ich wytwarzania, ich kompozycje farmaceutyczne i ich zastosowania |
| EP1676845B1 (en) | 1999-11-05 | 2008-06-11 | AstraZeneca AB | New quinazoline derivatives |
| US7498335B2 (en) | 2000-03-06 | 2009-03-03 | Astrazeneca Ab | Method of producing an antiangiogenic or vascular permeability reducing effect |
| EP1274692B1 (en) | 2000-04-07 | 2006-08-02 | AstraZeneca AB | Quinazoline compounds |
| NZ534171A (en) | 2002-02-01 | 2007-06-29 | Astrazeneca Ab | Quinazoline compounds for the treatment of diseases associated with angiogenesis and/or increased vascular permeability |
| TW200400034A (en) | 2002-05-20 | 2004-01-01 | Bristol Myers Squibb Co | Pyrazolo-pyrimidine aniline compounds useful as kinase inhibitors |
| NZ539408A (en) | 2002-11-04 | 2007-09-28 | Astrazeneca Ab | Quinazoline derivatives as SRC tyrosine kinase inhibitors for treating solid tumours |
| AU2008202205B2 (en) * | 2003-12-23 | 2009-09-10 | Pfizer Inc. | Novel quinoline derivatives |
| MXPA06007242A (es) | 2003-12-23 | 2006-08-18 | Pfizer | Nuevos derivados de quinolina. |
| JP4585978B2 (ja) * | 2005-03-03 | 2010-11-24 | 参天製薬株式会社 | キノリルアルキルチオ基を有する新規環式化合物 |
| KR20080027923A (ko) | 2005-08-08 | 2008-03-28 | 화이자 인코포레이티드 | Ｖｅｇｆ-ｒ 억제제의 염 및 다형체 |
| US20080190689A1 (en) * | 2007-02-12 | 2008-08-14 | Ballard Ebbin C | Inserts for engine exhaust systems |
| SG10201510586PA (en) | 2008-06-30 | 2016-01-28 | Mesoblast Inc | Treatment of Eye Diseases And Excessive Neovascularization Using A Combined Therapy |
| CN101723894B (zh) * | 2009-12-03 | 2011-12-28 | 南京大学 | N-喹啉酰胺类衍生物及其制法与用途 |
| SG192769A1 (en) | 2011-03-04 | 2013-09-30 | Glaxosmithkline Ip No 2 Ltd | Amino-quinolines as kinase inhibitors |
| TWI547494B (zh) | 2011-08-18 | 2016-09-01 | 葛蘭素史克智慧財產發展有限公司 | 作為激酶抑制劑之胺基喹唑啉類 |
| AR092530A1 (es) | 2012-09-13 | 2015-04-22 | Glaxosmithkline Llc | Compuesto de amino-quinolina, composicion farmaceutica que lo comprende y uso de dicho compuesto para la preparacion de un medicamento |
| TWI592417B (zh) | 2012-09-13 | 2017-07-21 | 葛蘭素史克智慧財產發展有限公司 | 胺基喹唑啉激酶抑制劑之前藥 |
| HK1217092A1 (zh) | 2013-02-15 | 2016-12-23 | Kala Pharmaceuticals, Inc. | 治疗性化合物及其用途 |
| US9688688B2 (en) | 2013-02-20 | 2017-06-27 | Kala Pharmaceuticals, Inc. | Crystalline forms of 4-((4-((4-fluoro-2-methyl-1H-indol-5-yl)oxy)-6-methoxyquinazolin-7-yl)oxy)-1-(2-oxa-7-azaspiro[3.5]nonan-7-yl)butan-1-one and uses thereof |
| CN105189462B (zh) | 2013-02-20 | 2017-11-10 | 卡拉制药公司 | 治疗性化合物和其用途 |
| JP6301374B2 (ja) | 2013-02-21 | 2018-03-28 | グラクソスミスクライン、インテレクチュアル、プロパティー、ディベロップメント、リミテッドＧｌａｘｏｓｍｉｔｈｋｌｉｎｅ Ｉｎｔｅｌｌｅｃｔｕａｌ Ｐｒｏｐｅｒｔｙ Ｄｅｖｅｌｏｐｍｅｎｔ Ｌｉｍｉｔｅｄ | キナーゼ阻害剤としてのキナゾリン類 |
| AU2014342042B2 (en) | 2013-11-01 | 2017-08-17 | KALA BIO, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| US9890173B2 (en) | 2013-11-01 | 2018-02-13 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| CN112028825B (zh) * | 2015-04-07 | 2025-03-14 | 广东众生睿创生物科技有限公司 | 酪氨酸激酶抑制剂及包含该酪氨酸激酶抑制剂的药物组合物 |
| CA3012718A1 (en) | 2016-02-08 | 2017-08-17 | Vitrisa Therapeutics, Inc. | Compositions with improved intravitreal half-life and uses thereof |
| CA3036336A1 (en) | 2016-09-08 | 2018-03-15 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| CA3036340A1 (en) | 2016-09-08 | 2018-03-15 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| WO2018048746A1 (en) | 2016-09-08 | 2018-03-15 | Kala Pharmaceuticals, Inc. | Crystalline forms of therapeutic compounds and uses thereof |
| WO2018064465A1 (en) | 2016-09-29 | 2018-04-05 | The Regents Of The University Of California | Compounds for increasing neural plasticity |
| CA3130770A1 (en) | 2019-02-27 | 2020-09-03 | The Regents Of The University Of California | Azepino-indoles and other heterocycles for treating brain disorders |
| EP4091613A4 (en) * | 2020-01-19 | 2024-02-21 | Chia Tai Tianqing Pharmaceutical Group Co., Ltd. | QUINOLINE DERIVATIVE FOR TREATING RHEUMATOID ARTHRITIS |
| TW202333668A (zh) | 2021-12-15 | 2023-09-01 | 美商德利克斯醫療公司 | 經苯氧基及苄氧基取代之精神成形素(psychoplastogen)及其用途 |
| CN120289432B (zh) * | 2025-06-12 | 2025-09-05 | 上海健康医学院 | 一种具有极光激酶b和表皮生长因子受体双重抑制作用的喹啉类化合物及用途 |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3755332A (en) * | 1971-07-01 | 1973-08-28 | Ciba Geigy Corp | Substituted 4 indazolaminoquinolines |
| EP0860433A1 (en) * | 1995-11-07 | 1998-08-26 | Kirin Beer Kabushiki Kaisha | Quinoline derivatives and quinazoline derivatives inhibiting autophosphorylation of growth factor receptor originating in platelet and pharmaceutical compositions containing the same |
| CN1237963A (zh) * | 1996-09-25 | 1999-12-08 | 曾尼卡有限公司 | 抑制生长因子如vegf的作用的喹啉衍生物 |
| WO2000018761A1 (en) * | 1998-09-29 | 2000-04-06 | American Cyanamid Company | Substituted 3-cyanoquinolines as protein tyrosine kinases inhibitors |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US36256A (en) * | 1862-08-19 | Improvement in sewing-m ach ines | ||
| IL81307A0 (en) | 1986-01-23 | 1987-08-31 | Union Carbide Agricult | Method for reducing moisture loss from plants and increasing crop yield utilizing nitrogen containing heterocyclic compounds and some novel polysubstituted pyridine derivatives |
| IL89029A (en) | 1988-01-29 | 1993-01-31 | Lilly Co Eli | Fungicidal quinoline and cinnoline derivatives, compositions containing them, and fungicidal methods of using them |
| WO1992020642A1 (en) | 1991-05-10 | 1992-11-26 | Rhone-Poulenc Rorer International (Holdings) Inc. | Bis mono-and bicyclic aryl and heteroaryl compounds which inhibit egf and/or pdgf receptor tyrosine kinase |
| US5480883A (en) | 1991-05-10 | 1996-01-02 | Rhone-Poulenc Rorer Pharmaceuticals Inc. | Bis mono- and bicyclic aryl and heteroaryl compounds which inhibit EGF and/or PDGF receptor tyrosine kinase |
| IL117620A0 (en) | 1995-03-27 | 1996-07-23 | Fujisawa Pharmaceutical Co | Heterocyclic compounds processes for the preparation thereof and pharmaceutical compositions containing the same |
| GB9514265D0 (en) | 1995-07-13 | 1995-09-13 | Wellcome Found | Hetrocyclic compounds |
| AR007857A1 (es) | 1996-07-13 | 1999-11-24 | Glaxo Group Ltd | Compuestos heterociclicos fusionados como inhibidores de proteina tirosina quinasa, sus metodos de preparacion, intermediarios uso en medicina ycomposiciones farmaceuticas que los contienen. |
| JP4073961B2 (ja) | 1996-10-01 | 2008-04-09 | 協和醗酵工業株式会社 | 含窒素複素環化合物 |
| US6002008A (en) | 1997-04-03 | 1999-12-14 | American Cyanamid Company | Substituted 3-cyano quinolines |
| EP0984692A4 (en) | 1997-05-30 | 2001-02-21 | Merck & Co Inc | ANGIOGENESIS INHIBITORS |
| US6162804A (en) | 1997-09-26 | 2000-12-19 | Merck & Co., Inc. | Tyrosine kinase inhibitors |
| GB9721437D0 (en) | 1997-10-10 | 1997-12-10 | Glaxo Group Ltd | Heteroaromatic compounds and their use in medicine |
| GB9800575D0 (en) | 1998-01-12 | 1998-03-11 | Glaxo Group Ltd | Heterocyclic compounds |
| RS49779B (sr) | 1998-01-12 | 2008-06-05 | Glaxo Group Limited, | Biciklična heteroaromatična jedinjenja kao inhibitori protein tirozin kinaze |
| US6184226B1 (en) | 1998-08-28 | 2001-02-06 | Scios Inc. | Quinazoline derivatives as inhibitors of P-38 α |
| GB2345486A (en) | 1999-01-11 | 2000-07-12 | Glaxo Group Ltd | Heteroaromatic protein tyrosine kinase inhibitors |
| UA71945C2 (en) | 1999-01-27 | 2005-01-17 | Pfizer Prod Inc | Substituted bicyclic derivatives being used as anticancer agents |
| JP3270834B2 (ja) | 1999-01-27 | 2002-04-02 | ファイザー・プロダクツ・インク | 抗がん剤として有用なヘテロ芳香族二環式誘導体 |
| PE20010306A1 (es) | 1999-07-02 | 2001-03-29 | Agouron Pharma | Compuestos de indazol y composiciones farmaceuticas que los contienen utiles para la inhibicion de proteina kinasa |
-
2001
- 2001-08-08 BR BR0113056-0A patent/BR0113056A/pt not_active Application Discontinuation
- 2001-08-08 IL IL15394701A patent/IL153947A0/xx unknown
- 2001-08-08 AU AU2001276536A patent/AU2001276536B2/en not_active Ceased
- 2001-08-08 US US10/332,274 patent/US7371765B2/en not_active Expired - Fee Related
- 2001-08-08 WO PCT/GB2001/003553 patent/WO2002012226A1/en not_active Ceased
- 2001-08-08 JP JP2002518201A patent/JP2004505964A/ja active Pending
- 2001-08-08 AU AU7653601A patent/AU7653601A/xx active Pending
- 2001-08-08 KR KR10-2003-7001934A patent/KR20030036686A/ko not_active Abandoned
- 2001-08-08 EP EP01954192A patent/EP1313726A1/en not_active Withdrawn
- 2001-08-08 CA CA002415469A patent/CA2415469A1/en not_active Abandoned
- 2001-08-08 CN CNB018139000A patent/CN1315822C/zh not_active Expired - Fee Related
- 2001-08-08 NZ NZ523358A patent/NZ523358A/en unknown
- 2001-08-08 MX MXPA03000252A patent/MXPA03000252A/es not_active Application Discontinuation
-
2003
- 2003-01-08 ZA ZA200300217A patent/ZA200300217B/en unknown
- 2003-01-14 IL IL153947A patent/IL153947A/en not_active IP Right Cessation
- 2003-02-07 NO NO20030625A patent/NO326315B1/no not_active IP Right Cessation
-
2007
- 2007-11-29 US US11/947,533 patent/US20080312273A1/en not_active Abandoned
Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3755332A (en) * | 1971-07-01 | 1973-08-28 | Ciba Geigy Corp | Substituted 4 indazolaminoquinolines |
| EP0860433A1 (en) * | 1995-11-07 | 1998-08-26 | Kirin Beer Kabushiki Kaisha | Quinoline derivatives and quinazoline derivatives inhibiting autophosphorylation of growth factor receptor originating in platelet and pharmaceutical compositions containing the same |
| CN1237963A (zh) * | 1996-09-25 | 1999-12-08 | 曾尼卡有限公司 | 抑制生长因子如vegf的作用的喹啉衍生物 |
| WO2000018761A1 (en) * | 1998-09-29 | 2000-04-06 | American Cyanamid Company | Substituted 3-cyanoquinolines as protein tyrosine kinases inhibitors |
Also Published As
| Publication number | Publication date |
|---|---|
| AU7653601A (en) | 2002-02-18 |
| NO20030625L (no) | 2003-02-07 |
| ZA200300217B (en) | 2004-04-08 |
| IL153947A0 (en) | 2003-07-31 |
| US20080312273A1 (en) | 2008-12-18 |
| EP1313726A1 (en) | 2003-05-28 |
| CN1446212A (zh) | 2003-10-01 |
| CA2415469A1 (en) | 2002-02-14 |
| US20030199491A1 (en) | 2003-10-23 |
| WO2002012226A1 (en) | 2002-02-14 |
| MXPA03000252A (es) | 2003-06-06 |
| KR20030036686A (ko) | 2003-05-09 |
| US7371765B2 (en) | 2008-05-13 |
| NO20030625D0 (no) | 2003-02-07 |
| JP2004505964A (ja) | 2004-02-26 |
| NZ523358A (en) | 2004-09-24 |
| AU2001276536B2 (en) | 2007-01-04 |
| NO326315B1 (no) | 2008-11-10 |
| AU2001276536B9 (en) | 2002-02-18 |
| BR0113056A (pt) | 2003-07-08 |
| IL153947A (en) | 2008-12-29 |
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