CA2916504A1 - Carbazole carboxamide compounds useful as kinase inhibitors - Google Patents
Carbazole carboxamide compounds useful as kinase inhibitors Download PDFInfo
- Publication number
- CA2916504A1 CA2916504A1 CA2916504A CA2916504A CA2916504A1 CA 2916504 A1 CA2916504 A1 CA 2916504A1 CA 2916504 A CA2916504 A CA 2916504A CA 2916504 A CA2916504 A CA 2916504A CA 2916504 A1 CA2916504 A1 CA 2916504A1
- Authority
- CA
- Canada
- Prior art keywords
- carbazole
- carboxamide
- mixture
- dioxo
- mmol
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Abandoned
Links
- GFHHIWFKWFBNRU-UHFFFAOYSA-N 9h-carbazole-1-carboxamide Chemical class C12=CC=CC=C2NC2=C1C=CC=C2C(=O)N GFHHIWFKWFBNRU-UHFFFAOYSA-N 0.000 title description 6
- 229940043355 kinase inhibitor Drugs 0.000 title description 4
- 239000003757 phosphotransferase inhibitor Substances 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 300
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 85
- 150000003839 salts Chemical class 0.000 claims abstract description 81
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 29
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 29
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims abstract description 25
- 208000023275 Autoimmune disease Diseases 0.000 claims abstract description 18
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims abstract description 6
- 238000011282 treatment Methods 0.000 claims description 38
- 239000003814 drug Substances 0.000 claims description 21
- 239000003937 drug carrier Substances 0.000 claims description 13
- 238000004519 manufacturing process Methods 0.000 claims description 13
- 238000002560 therapeutic procedure Methods 0.000 claims description 4
- VIRRHNLXPOCKII-UHFFFAOYSA-N 4-[3-(5-fluoro-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-7-(methoxymethyl)-9h-carbazole-1-carboxamide Chemical compound O=C1C=C2C(F)=CC=CN2C(=O)N1C1=C(C)C(C=2C=CC(=C3NC=4C(C=23)=CC=C(C=4)COC)C(N)=O)=CC=C1 VIRRHNLXPOCKII-UHFFFAOYSA-N 0.000 claims 4
- AXNKUCHUGAZVMO-UHFFFAOYSA-N 4-[3-(5-fluoro-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(C(C)(C)O)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(C)C(N2C(N3C=CC=C(F)C3=CC2=O)=O)=CC=C1 AXNKUCHUGAZVMO-UHFFFAOYSA-N 0.000 claims 3
- BPINSDADQGFXNS-UHFFFAOYSA-N 4-[2-chloro-3-(1-methyl-2,4-dioxoquinazolin-3-yl)phenyl]-7-(2-hydroxypropan-2-yl)-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(C(C)(C)O)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(Cl)C(N2C(=O)C3=CC=CC=C3N(C2=O)C)=CC=C1 BPINSDADQGFXNS-UHFFFAOYSA-N 0.000 claims 2
- KXUXXPNDCAWJHM-UHFFFAOYSA-N 4-[2-chloro-3-(8-fluoro-1-methyl-2,4-dioxoquinazolin-3-yl)phenyl]-7-(2-hydroxypropan-2-yl)-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(C(C)(C)O)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(Cl)C(N2C(=O)C3=CC=CC(F)=C3N(C2=O)C)=CC=C1 KXUXXPNDCAWJHM-UHFFFAOYSA-N 0.000 claims 2
- IWVCATOVLJOXMB-UHFFFAOYSA-N 4-[3-(4-fluoro-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(C(C)(C)O)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(C)C(N2C(N3C=CC=CC3=C(F)C2=O)=O)=CC=C1 IWVCATOVLJOXMB-UHFFFAOYSA-N 0.000 claims 2
- FFVSEFDDGUYDFO-UHFFFAOYSA-N 4-[3-(5,7-dioxo-[1,3]thiazolo[3,2-c]pyrimidin-6-yl)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(C(C)(C)O)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(C)C(N2C(N3C=CSC3=CC2=O)=O)=CC=C1 FFVSEFDDGUYDFO-UHFFFAOYSA-N 0.000 claims 2
- XAJGLHVYSGTVTF-UHFFFAOYSA-N 4-[3-(5-chloro-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-7-(2,2-dimethylpropanoylamino)-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(NC(=O)C(C)(C)C)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(C)C(N2C(N3C=CC=C(Cl)C3=CC2=O)=O)=CC=C1 XAJGLHVYSGTVTF-UHFFFAOYSA-N 0.000 claims 2
- RXHAROKPHMWUME-UHFFFAOYSA-N 4-[3-(5-chloro-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(C(C)(C)O)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(C)C(N2C(N3C=CC=C(Cl)C3=CC2=O)=O)=CC=C1 RXHAROKPHMWUME-UHFFFAOYSA-N 0.000 claims 2
- RNLHORWOBQSYJE-UHFFFAOYSA-N 4-[3-(5-chloro-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-7-(methoxymethyl)-9h-carbazole-1-carboxamide Chemical compound O=C1C=C2C(Cl)=CC=CN2C(=O)N1C1=C(C)C(C=2C=CC(=C3NC=4C(C=23)=CC=C(C=4)COC)C(N)=O)=CC=C1 RNLHORWOBQSYJE-UHFFFAOYSA-N 0.000 claims 2
- BEKXRKQECXXKGJ-UHFFFAOYSA-N 4-[3-(5-chloro-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-7-(pyrrolidin-1-ylmethyl)-9h-carbazole-1-carboxamide Chemical compound C1=CC=C(N2C(N3C=CC=C(Cl)C3=CC2=O)=O)C(C)=C1C(C=1C2=CC=3)=CC=C(C(N)=O)C=1NC2=CC=3CN1CCCC1 BEKXRKQECXXKGJ-UHFFFAOYSA-N 0.000 claims 2
- JPJRIRSPLLYPRY-UHFFFAOYSA-N 4-[3-(5-fluoro-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-7-(hydroxymethyl)-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(CO)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(C)C(N2C(N3C=CC=C(F)C3=CC2=O)=O)=CC=C1 JPJRIRSPLLYPRY-UHFFFAOYSA-N 0.000 claims 2
- KQUDGOWUGZTCKG-UHFFFAOYSA-N 4-[3-(6-fluoro-1-methyl-2,4-dioxoquinazolin-3-yl)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(C(C)(C)O)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(C)C(N2C(C3=CC(F)=CC=C3N(C)C2=O)=O)=CC=C1 KQUDGOWUGZTCKG-UHFFFAOYSA-N 0.000 claims 2
- BEVUBRZINAWGDH-UHFFFAOYSA-N 4-[3-(8-fluoro-1-methyl-2,4-dioxoquinazolin-3-yl)-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-5-methyl-9h-carbazole-1-carboxamide Chemical compound O=C1N(C)C2=C(F)C=CC=C2C(=O)N1C1=C(C)C(C=2C=CC(=C3NC=4C=C(C=C(C=4C3=2)C)C(C)(C)O)C(N)=O)=CC=C1 BEVUBRZINAWGDH-UHFFFAOYSA-N 0.000 claims 2
- OPCHAIUSSHIEQR-UHFFFAOYSA-N 4-[3-[3-(4-fluorophenyl)-2,6-dioxopyrimidin-1-yl]-2-methylphenyl]-7-(2-hydroxypropan-2-yl)-9h-carbazole-1-carboxamide Chemical compound CC1=C(C=2C=3C4=CC=C(C=C4NC=3C(C(N)=O)=CC=2)C(C)(C)O)C=CC=C1N(C1=O)C(=O)C=CN1C1=CC=C(F)C=C1 OPCHAIUSSHIEQR-UHFFFAOYSA-N 0.000 claims 2
- YSLQGJFYBNLPDI-UHFFFAOYSA-N 7-(2-hydroxypropan-2-yl)-4-[3-(5-methoxy-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(C(C)(C)O)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(C)C(N2C(=O)C=C3N(C2=O)C=CC=C3OC)=CC=C1 YSLQGJFYBNLPDI-UHFFFAOYSA-N 0.000 claims 2
- HPPFVYVYCRLUIG-UHFFFAOYSA-N 7-(2-hydroxypropan-2-yl)-4-[3-(6-methoxy-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(C(C)(C)O)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(C)C(N2C(=O)C=C3N(C2=O)C=CC(=C3)OC)=CC=C1 HPPFVYVYCRLUIG-UHFFFAOYSA-N 0.000 claims 2
- HMFXPCSTCHRNIX-UHFFFAOYSA-N 7-(2-hydroxypropan-2-yl)-4-[3-(7-methoxy-1,3-dioxopyrido[1,2-c]pyrimidin-2-yl)-2-methylphenyl]-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(C(C)(C)O)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(C)C(N2C(=O)C=C3C=CC(=CN3C2=O)OC)=CC=C1 HMFXPCSTCHRNIX-UHFFFAOYSA-N 0.000 claims 2
- RAGWYGVSFHQCQZ-UHFFFAOYSA-N 7-(2-hydroxypropan-2-yl)-4-[3-(8-methoxy-1-methyl-2,4-dioxoquinazolin-3-yl)-2-methylphenyl]-9h-carbazole-1-carboxamide Chemical compound N1C2=CC(C(C)(C)O)=CC=C2C2=C1C(C(N)=O)=CC=C2C1=C(C)C(N2C(=O)N(C)C3=C(C2=O)C=CC=C3OC)=CC=C1 RAGWYGVSFHQCQZ-UHFFFAOYSA-N 0.000 claims 2
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Classifications
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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
- C07D403/10—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 aromatic rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
- C07D513/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00
- C07D513/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for in groups C07D463/00, C07D477/00 or C07D499/00 - C07D507/00 in which the condensed system contains two hetero rings
- C07D513/04—Ortho-condensed systems
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
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- Pharmacology & Pharmacy (AREA)
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- Immunology (AREA)
- Pain & Pain Management (AREA)
- Rheumatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
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| US201361839130P | 2013-06-25 | 2013-06-25 | |
| US61/839,130 | 2013-06-25 | ||
| PCT/US2014/043980 WO2014210087A1 (en) | 2013-06-25 | 2014-06-25 | Carbazole carboxamide compounds useful as kinase inhibitors |
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| CA2916504A1 true CA2916504A1 (en) | 2014-12-31 |
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| EP (1) | EP3013815B1 (enExample) |
| JP (1) | JP6353530B2 (enExample) |
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| CN (1) | CN105473573B (enExample) |
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| MX (1) | MX2015016771A (enExample) |
| SG (1) | SG11201510028PA (enExample) |
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| LT3209651T (lt) * | 2014-10-24 | 2020-01-10 | Bristol-Myers Squibb Company | Karbazolo dariniai |
| LT3461821T (lt) | 2014-10-24 | 2020-08-10 | Bristol-Myers Squibb Company | Indolo karboksamido junginiai, naudotini kaip kinazės inhibitoriai |
| AU2015335783B2 (en) | 2014-10-24 | 2019-10-03 | Bristol-Myers Squibb Company | Tricyclic atropisomer compounds |
| CN105802100A (zh) * | 2016-04-22 | 2016-07-27 | 宁波硫华聚合物有限公司 | 橡胶促进剂粘合剂六甲氧基甲基蜜胺预分散母胶粒及其制备方法 |
| CN105670057A (zh) * | 2016-04-25 | 2016-06-15 | 无锡智谷锐拓技术服务有限公司 | 一种耐油橡胶的制备方法 |
| CN105694150A (zh) * | 2016-04-25 | 2016-06-22 | 无锡智谷锐拓技术服务有限公司 | 一种耐油橡胶 |
| CN106084903A (zh) * | 2016-06-02 | 2016-11-09 | 扬州兰都塑料科技有限公司 | 一种电缆外部涂覆的水性防火涂料的制备方法 |
| CN105907150A (zh) * | 2016-06-02 | 2016-08-31 | 扬州兰都塑料科技有限公司 | 一种电缆涂料用阻燃剂 |
| CN106045972B (zh) * | 2016-06-03 | 2018-11-16 | 中山大学 | 咔唑-利凡斯的明二联体及其药物组合物和应用 |
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| CN115232061B (zh) * | 2021-09-18 | 2024-01-30 | 山西紫罗蓝新材料科技有限公司 | 一种3-硝基-9-乙基咔唑粗产物的提取工艺 |
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| US4200750A (en) | 1977-01-07 | 1980-04-29 | Westwood Pharmaceuticals Inc. | 4-Substituted imidazo [1,2-a]quinoxalines |
| CA2140722A1 (en) | 1994-01-24 | 1995-07-25 | Joseph A. Jakubowski | Beta-carboline thromboxane synthase inhibitors |
| US7405295B2 (en) | 2003-06-04 | 2008-07-29 | Cgi Pharmaceuticals, Inc. | Certain imidazo[1,2-a]pyrazin-8-ylamines and method of inhibition of Bruton's tyrosine kinase by such compounds |
| US7393848B2 (en) | 2003-06-30 | 2008-07-01 | Cgi Pharmaceuticals, Inc. | Certain heterocyclic substituted imidazo[1,2-A]pyrazin-8-ylamines and methods of inhibition of Bruton's tyrosine kinase by such compounds |
| WO2005047290A2 (en) | 2003-11-11 | 2005-05-26 | Cellular Genomics Inc. | Imidazo[1,2-a] pyrazin-8-ylamines as kinase inhibitors |
| WO2006044687A2 (en) | 2004-10-15 | 2006-04-27 | Takeda San Diego, Inc. | Kinase inhibitors |
| SG159549A1 (en) | 2004-11-10 | 2010-03-30 | Cgi Pharmaceuticals Inc | Imidazo[1,2-a] pyrazin-8-ylamines useful as modulators of kinase activity |
| PL1831227T3 (pl) | 2004-12-17 | 2013-10-31 | Glenmark Pharmaceuticals Sa | Nowe związki heterocykliczne użyteczne w leczeniu stanów zapalnych i dolegliwości alergicznych |
| AU2006223409B2 (en) | 2005-03-10 | 2011-07-21 | Gilead Connecticut, Inc. | Certain substituted amides, method of making, and method of use thereof |
| US20070078136A1 (en) | 2005-09-22 | 2007-04-05 | Bristol-Myers Squibb Company | Fused heterocyclic compounds useful as kinase modulators |
| US7723336B2 (en) | 2005-09-22 | 2010-05-25 | Bristol-Myers Squibb Company | Fused heterocyclic compounds useful as kinase modulators |
| ES2390135T3 (es) | 2005-11-22 | 2012-11-06 | Merck Sharp & Dohme Corp. | Compuestos tricíclicos útiles como inhibidores de quinasas |
| JP2010502751A (ja) | 2006-09-11 | 2010-01-28 | シージーアイ ファーマシューティカルズ，インコーポレイティド | キナーゼ阻害物質、およびキナーゼ阻害物質の使用および同定方法 |
| CA2663178C (en) | 2006-09-11 | 2016-01-12 | Matrix Laboratories Ltd. | Dibenzofuran derivatives as inhibitors of pde-4 and pde-10 |
| US20090062251A1 (en) | 2007-08-17 | 2009-03-05 | Astrazeneca Ab | Novel Compounds 002 |
| US8431569B2 (en) | 2007-12-13 | 2013-04-30 | Merck Sharp & Dohme Corp. | Inhibitors of janus kinases |
| US20110046378A1 (en) | 2008-02-14 | 2011-02-24 | Siemens Medical Solutions Usa, Inc. | Novel Imaging Agents for Detecting Neurological Dysfunction |
| GB0809360D0 (en) | 2008-05-22 | 2008-07-02 | Isis Innovation | Calcium modulation |
| CA2725512C (en) * | 2008-07-18 | 2016-06-28 | F. Hoffmann-La Roche Ag | Novel phenylimidazopyrazines |
| EP2151441A1 (en) | 2008-08-06 | 2010-02-10 | Julius-Maximilians-Universität Würzburg | Beta-carbolin-derivates as substrates for an enzyme |
| PE20110819A1 (es) * | 2008-12-19 | 2011-11-02 | Bristol Myers Squibb Co | Compuestos de carbazol carboxamida utiles como inhibidores de cinasa |
| CN101475571B (zh) | 2009-01-21 | 2011-06-22 | 中国药科大学 | β-咔啉类细胞周期蛋白依赖性激酶2抑制剂及其用途 |
| US8242260B2 (en) | 2009-08-28 | 2012-08-14 | Novartis Ag | Compounds and compositions as protein kinase inhibitors |
| US8685969B2 (en) | 2010-06-16 | 2014-04-01 | Bristol-Myers Squibb Company | Carboline carboxamide compounds useful as kinase inhibitors |
| EP2455378A1 (en) | 2010-11-03 | 2012-05-23 | Philip Morris Products S.A. | Carbazole and carboline derivatives, and preparation and therapeutic applications thereof |
| AU2011330850B2 (en) | 2010-11-15 | 2016-01-28 | Viiv Healthcare Uk Limited | Inhibitors of HIV replication |
| WO2012156334A1 (en) | 2011-05-17 | 2012-11-22 | F. Hoffmann-La Roche Ag | Inhibitors of bruton's tyrosine kinase |
| AR096721A1 (es) | 2013-06-25 | 2016-01-27 | Bristol Myers Squibb Co | Compuestos de tetrahidrocarbazol y carbazol carboxamida sustituidos |
-
2014
- 2014-06-25 AU AU2014302550A patent/AU2014302550A1/en not_active Abandoned
- 2014-06-25 CA CA2916504A patent/CA2916504A1/en not_active Abandoned
- 2014-06-25 WO PCT/US2014/043980 patent/WO2014210087A1/en not_active Ceased
- 2014-06-25 EA EA201690012A patent/EA025863B1/ru not_active IP Right Cessation
- 2014-06-25 BR BR112015031432A patent/BR112015031432A2/pt not_active Application Discontinuation
- 2014-06-25 JP JP2016523870A patent/JP6353530B2/ja not_active Expired - Fee Related
- 2014-06-25 SG SG11201510028PA patent/SG11201510028PA/en unknown
- 2014-06-25 US US14/392,355 patent/US9714234B2/en active Active
- 2014-06-25 CN CN201480046669.2A patent/CN105473573B/zh not_active Expired - Fee Related
- 2014-06-25 EP EP14740096.4A patent/EP3013815B1/en not_active Not-in-force
- 2014-06-25 KR KR1020167001634A patent/KR102345381B1/ko not_active Expired - Fee Related
- 2014-06-25 MX MX2015016771A patent/MX2015016771A/es unknown
-
2015
- 2015-12-22 IL IL243295A patent/IL243295A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| US9714234B2 (en) | 2017-07-25 |
| CN105473573B (zh) | 2018-03-16 |
| SG11201510028PA (en) | 2016-01-28 |
| EP3013815A1 (en) | 2016-05-04 |
| CN105473573A (zh) | 2016-04-06 |
| EA025863B1 (ru) | 2017-02-28 |
| JP2016523908A (ja) | 2016-08-12 |
| WO2014210087A1 (en) | 2014-12-31 |
| BR112015031432A2 (pt) | 2017-07-25 |
| US20160200710A1 (en) | 2016-07-14 |
| IL243295A0 (en) | 2016-02-29 |
| AU2014302550A1 (en) | 2016-02-11 |
| EP3013815B1 (en) | 2017-05-03 |
| MX2015016771A (es) | 2016-03-31 |
| JP6353530B2 (ja) | 2018-07-04 |
| KR102345381B1 (ko) | 2021-12-29 |
| EA201690012A1 (ru) | 2016-05-31 |
| KR20160022890A (ko) | 2016-03-02 |
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