CA2948582A1 - Carboxamide derivatives - Google Patents
Carboxamide derivatives Download PDFInfo
- Publication number
- CA2948582A1 CA2948582A1 CA2948582A CA2948582A CA2948582A1 CA 2948582 A1 CA2948582 A1 CA 2948582A1 CA 2948582 A CA2948582 A CA 2948582A CA 2948582 A CA2948582 A CA 2948582A CA 2948582 A1 CA2948582 A1 CA 2948582A1
- Authority
- CA
- Canada
- Prior art keywords
- methyl
- pyrazol
- dihydro
- triazole
- oxo
- 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
- 229940053202 antiepileptics carboxamide derivative Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 202
- 150000003839 salts Chemical class 0.000 claims abstract description 101
- 238000000034 method Methods 0.000 claims abstract description 100
- 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 23
- 238000004519 manufacturing process Methods 0.000 claims abstract description 5
- 239000013543 active substance Substances 0.000 claims abstract description 4
- 206010064911 Pulmonary arterial hypertension Diseases 0.000 claims description 70
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 69
- -1 chloro, fluoro, cyclopropyl Chemical group 0.000 claims description 49
- 201000010099 disease Diseases 0.000 claims description 47
- 238000011282 treatment Methods 0.000 claims description 39
- 239000003814 drug Substances 0.000 claims description 33
- 208000002815 pulmonary hypertension Diseases 0.000 claims description 28
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 27
- 206010016654 Fibrosis Diseases 0.000 claims description 26
- 230000004761 fibrosis Effects 0.000 claims description 25
- 230000035876 healing Effects 0.000 claims description 23
- 208000035475 disorder Diseases 0.000 claims description 22
- 208000010412 Glaucoma Diseases 0.000 claims description 21
- 208000006673 asthma Diseases 0.000 claims description 21
- 125000005843 halogen group Chemical group 0.000 claims description 20
- 201000001474 proteinuria Diseases 0.000 claims description 20
- 230000029663 wound healing Effects 0.000 claims description 20
- 208000010392 Bone Fractures Diseases 0.000 claims description 19
- 208000031953 Hereditary hemorrhagic telangiectasia Diseases 0.000 claims description 19
- 206010017076 Fracture Diseases 0.000 claims description 17
- 230000000694 effects Effects 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 10
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 9
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 8
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 8
- 239000003937 drug carrier Substances 0.000 claims description 8
- 125000001424 substituent group Chemical group 0.000 claims description 7
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 6
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 6
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 6
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 5
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 5
- 125000006536 (C1-C2)alkoxy group Chemical group 0.000 claims description 4
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 4
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 4
- 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 3
- 125000006529 (C3-C6) alkyl group Chemical group 0.000 claims description 2
- 125000004198 2-fluorophenyl group Chemical group [H]C1=C([H])C(F)=C(*)C([H])=C1[H] 0.000 claims description 2
- 125000002785 azepinyl group Chemical group 0.000 claims description 2
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
- MOKGJPFJPBCJGY-UHFFFAOYSA-N 1-(2,4-dichlorophenyl)-N-[1-(2-fluorophenyl)-2,3-dimethyl-5-oxopyrazol-4-yl]-5-methyltriazole-4-carboxamide Chemical compound ClC1=C(C=CC(=C1)Cl)N1N=NC(=C1C)C(=O)NC=1C(N(N(C1C)C)C1=C(C=CC=C1)F)=O MOKGJPFJPBCJGY-UHFFFAOYSA-N 0.000 claims 1
- DJCHYTWZRDUVHQ-UHFFFAOYSA-N 1-(2-chloro-4-cyclopropylphenyl)-N-(1-cyclohexyl-2,3-dimethyl-5-oxopyrazol-4-yl)-5-methyltriazole-4-carboxamide Chemical compound ClC1=C(C=CC(=C1)C1CC1)N1N=NC(=C1C)C(=O)NC=1C(N(N(C1C)C)C1CCCCC1)=O DJCHYTWZRDUVHQ-UHFFFAOYSA-N 0.000 claims 1
- ACXUNKGGFBQCSH-UHFFFAOYSA-N 1-(2-chloro-4-cyclopropylphenyl)-N-[1-(2-fluorophenyl)-2,3-dimethyl-5-oxopyrazol-4-yl]-5-methyltriazole-4-carboxamide Chemical compound ClC1=C(C=CC(=C1)C1CC1)N1N=NC(=C1C)C(=O)NC=1C(N(N(C1C)C)C1=C(C=CC=C1)F)=O ACXUNKGGFBQCSH-UHFFFAOYSA-N 0.000 claims 1
- DJCHYTWZRDUVHQ-HPRDVNIFSA-N 1-(2-chloro-4-cyclopropylphenyl)-N-[1-cyclohexyl-3-methyl-5-oxo-2-(trideuteriomethyl)pyrazol-4-yl]-5-methyltriazole-4-carboxamide Chemical compound [2H]C([2H])([2H])N1N(C2CCCCC2)C(=O)C(NC(=O)C2=C(C)N(N=N2)C2=CC=C(C=C2Cl)C2CC2)=C1C DJCHYTWZRDUVHQ-HPRDVNIFSA-N 0.000 claims 1
- FODUFECSLYLXJO-UHFFFAOYSA-N 1-(2-chloro-4-methoxyphenyl)-N-(1-cyclohexyl-2,3-dimethyl-5-oxopyrazol-4-yl)-5-methyltriazole-4-carboxamide Chemical compound ClC1=C(C=CC(=C1)OC)N1N=NC(=C1C)C(=O)NC=1C(N(N(C1C)C)C1CCCCC1)=O FODUFECSLYLXJO-UHFFFAOYSA-N 0.000 claims 1
- ISFJQKFPHDUWPE-UHFFFAOYSA-N 1-(4-chloro-2-cyclopropylphenyl)-N-(1-cyclohexyl-2,3-dimethyl-5-oxopyrazol-4-yl)-5-methyltriazole-4-carboxamide Chemical compound ClC1=CC(=C(C=C1)N1N=NC(=C1C)C(=O)NC=1C(N(N(C1C)C)C1CCCCC1)=O)C1CC1 ISFJQKFPHDUWPE-UHFFFAOYSA-N 0.000 claims 1
- RZYISIGSIXJKBN-UHFFFAOYSA-N 1-(4-chloro-2-cyclopropylphenyl)-N-[1-(2-fluorophenyl)-2,3-dimethyl-5-oxopyrazol-4-yl]-5-methyltriazole-4-carboxamide Chemical compound ClC1=CC(=C(C=C1)N1N=NC(=C1C)C(=O)NC=1C(N(N(C1C)C)C1=C(C=CC=C1)F)=O)C1CC1 RZYISIGSIXJKBN-UHFFFAOYSA-N 0.000 claims 1
- KSOXQHSQZWSLIA-UHFFFAOYSA-N 1-(4-chlorophenyl)-N-(1-cyclohexyl-2,3-dimethyl-5-oxopyrazol-4-yl)-5-methyltriazole-4-carboxamide Chemical compound ClC1=CC=C(C=C1)N1N=NC(=C1C)C(=O)NC=1C(N(N(C1C)C)C1CCCCC1)=O KSOXQHSQZWSLIA-UHFFFAOYSA-N 0.000 claims 1
- SQLLXHARKNGURD-UHFFFAOYSA-N 1-(4-chlorophenyl)-N-[1-(2-fluorophenyl)-2,3-dimethyl-5-oxopyrazol-4-yl]-5-methyltriazole-4-carboxamide Chemical compound ClC1=CC=C(C=C1)N1N=NC(=C1C)C(=O)NC=1C(N(N(C1C)C)C1=C(C=CC=C1)F)=O SQLLXHARKNGURD-UHFFFAOYSA-N 0.000 claims 1
- WXVDTPRGJZKZPF-UHFFFAOYSA-N 1-[2-chloro-4-(trifluoromethoxy)phenyl]-N-(1-cyclohexyl-2,3-dimethyl-5-oxopyrazol-4-yl)-5-methyltriazole-4-carboxamide Chemical compound ClC1=C(C=CC(=C1)OC(F)(F)F)N1N=NC(=C1C)C(=O)NC=1C(N(N(C1C)C)C1CCCCC1)=O WXVDTPRGJZKZPF-UHFFFAOYSA-N 0.000 claims 1
- JMXMZZABLCOWIP-UHFFFAOYSA-N 1-[2-chloro-4-(trifluoromethoxy)phenyl]-N-[1-(2-fluorophenyl)-2,3-dimethyl-5-oxopyrazol-4-yl]-5-methyltriazole-4-carboxamide Chemical compound ClC1=C(C=CC(=C1)OC(F)(F)F)N1N=NC(=C1C)C(=O)NC=1C(N(N(C1C)C)C1=C(C=CC=C1)F)=O JMXMZZABLCOWIP-UHFFFAOYSA-N 0.000 claims 1
- LVMFPVUIWOOJNY-UHFFFAOYSA-N N-(1-cyclohexyl-2,3-dimethyl-5-oxopyrazol-4-yl)-1-(2,4-dichlorophenyl)-5-methyltriazole-4-carboxamide Chemical compound C1(CCCCC1)N1N(C(=C(C1=O)NC(=O)C=1N=NN(C1C)C1=C(C=C(C=C1)Cl)Cl)C)C LVMFPVUIWOOJNY-UHFFFAOYSA-N 0.000 claims 1
- LEXOBXPBMTWDHU-UHFFFAOYSA-N N-(1-cyclohexyl-2,3-dimethyl-5-oxopyrazol-4-yl)-1-(2-cyclopropyl-4-fluorophenyl)-5-methyltriazole-4-carboxamide Chemical compound C1(CCCCC1)N1N(C(=C(C1=O)NC(=O)C=1N=NN(C1C)C1=C(C=C(C=C1)F)C1CC1)C)C LEXOBXPBMTWDHU-UHFFFAOYSA-N 0.000 claims 1
- SMEJNAIKZQKEDP-UHFFFAOYSA-N N-(1-cyclohexyl-2,3-dimethyl-5-oxopyrazol-4-yl)-1-(4-methoxy-3-methylphenyl)-5-methyltriazole-4-carboxamide Chemical compound C1(CCCCC1)N1N(C(=C(C1=O)NC(=O)C=1N=NN(C1C)C1=CC(=C(C=C1)OC)C)C)C SMEJNAIKZQKEDP-UHFFFAOYSA-N 0.000 claims 1
- GPKSXWTVPBSUBX-UHFFFAOYSA-N N-(1-cyclohexyl-2,3-dimethyl-5-oxopyrazol-4-yl)-1-(4-methoxyphenyl)-5-methyltriazole-4-carboxamide Chemical compound C1(CCCCC1)N1N(C(=C(C1=O)NC(=O)C=1N=NN(C1C)C1=CC=C(C=C1)OC)C)C GPKSXWTVPBSUBX-UHFFFAOYSA-N 0.000 claims 1
- NGQWUQYESZDKHI-UHFFFAOYSA-N N-(1-cyclohexyl-2,3-dimethyl-5-oxopyrazol-4-yl)-1-[4-methoxy-2-(trifluoromethyl)phenyl]-5-methyltriazole-4-carboxamide Chemical compound C1(CCCCC1)N1N(C(=C(C1=O)NC(=O)C=1N=NN(C1C)C1=C(C=C(C=C1)OC)C(F)(F)F)C)C NGQWUQYESZDKHI-UHFFFAOYSA-N 0.000 claims 1
- NOVSDVCDYPGXAQ-UHFFFAOYSA-N N-(1-cyclohexyl-2,3-dimethyl-5-oxopyrazol-4-yl)-8-(trifluoromethoxy)-5,6-dihydro-4H-triazolo[1,5-a][1]benzazepine-3-carboxamide Chemical compound C1(CCCCC1)N1N(C(=C(C1=O)NC(=O)C=1N=NN2C1CCCC1=C2C=CC(=C1)OC(F)(F)F)C)C NOVSDVCDYPGXAQ-UHFFFAOYSA-N 0.000 claims 1
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
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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
- A61P9/12—Antihypertensives
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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
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
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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
-
- 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
- C07D413/02—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
-
- 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
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
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- General Health & Medical Sciences (AREA)
- Public Health (AREA)
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- Engineering & Computer Science (AREA)
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- Biomedical Technology (AREA)
- Vascular Medicine (AREA)
- Immunology (AREA)
- Dermatology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Plural Heterocyclic Compounds (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201461993046P | 2014-05-14 | 2014-05-14 | |
| EP14168319.3 | 2014-05-14 | ||
| EP14168319 | 2014-05-14 | ||
| US61/993,046 | 2014-05-14 | ||
| PCT/IB2015/001539 WO2015177646A1 (en) | 2014-05-14 | 2015-05-14 | Carboxamide derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2948582A1 true CA2948582A1 (en) | 2015-11-26 |
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|---|---|---|---|
| CA2948582A Abandoned CA2948582A1 (en) | 2014-05-14 | 2015-05-14 | Carboxamide derivatives |
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| EP (1) | EP3143014B1 (enExample) |
| JP (1) | JP6587637B2 (enExample) |
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| US9403810B2 (en) | 2014-05-14 | 2016-08-02 | Novartis Ag | Carboxamide derivatives |
| TW201623288A (zh) | 2014-05-14 | 2016-07-01 | 諾華公司 | 甲醯胺衍生物 |
| CN108007916B (zh) * | 2017-03-16 | 2020-08-04 | 黑龙江八一农垦大学 | 希尔伯特黄法建立稻株氮含量的共聚焦显微拉曼测量模型 |
| CN110749687B (zh) * | 2019-04-04 | 2021-05-28 | 中山大学 | 一种日本血吸虫病早期诊断尿液生物标志物及筛选方法和应用 |
| CN110038012B (zh) * | 2019-05-30 | 2021-06-11 | 济南大学 | 具有1,2,3-三氮唑结构片段的生物碱化合物在制备促血管生成药物中的应用 |
| DE102020116104A1 (de) | 2020-06-18 | 2021-12-23 | Charité - Universitätsmedizin Berlin, Körperschaft des öffentlichen Rechts | Metamizolderivate zur Prävention und Therapie der pulmonalen Hypertonie |
| CN113636977B (zh) * | 2021-09-01 | 2022-12-20 | 温州大学 | 2-芳基苯并氮杂卓及其衍生物的合成方法 |
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| IL147005A0 (en) * | 1999-06-11 | 2002-08-14 | Univ New York State Res Found | Antagonists of bmp and tgfb signaling pathways |
| US7354722B1 (en) | 1999-06-11 | 2008-04-08 | Signal Pharmaceuticals | Modulators of Smurf and BMP/TGFβ signaling pathways |
| WO2004078163A2 (en) | 2003-02-28 | 2004-09-16 | Transform Pharmaceuticals, Inc. | Pharmaceutical co-crystal compositions of drugs such as carbamazepine, celecoxib, olanzapine, itraconazole, topiramate, modafinil, 5-fluorouracil, hydrochlorothiazide, acetaminophen, aspirin, flurbiprofen, phenytoin and ibuprofen |
| GB0312368D0 (en) | 2003-05-30 | 2003-07-02 | Univ Aston | Novel ureido- and amido-pyrazolone derivatives |
| EP1667983A4 (en) | 2003-09-23 | 2010-07-21 | Merck Sharp & Dohme | PYRAZOL MODULATORS OF METABOTROPIC GLUTAMATE RECEPTORS |
| US7291743B2 (en) | 2005-03-29 | 2007-11-06 | Geneblue Corporation | Isoxazole derivatives and methods of treating nitric oxide mediated diseases |
| BRPI0618079A2 (pt) * | 2005-10-31 | 2011-08-16 | Biolipox Ab | composto ou um sal farmaceuticamente aceitável do mesmo, formulação farmacêutica, uso de um composto ou um sal farmaceuticamente aceitável do mesmo, método de tratamento de uma doença, produto de combinação, e, processos para a preparação de um composto, de uma formulação farmacêutica, e de um produto de combinação |
| WO2008121861A2 (en) | 2007-03-28 | 2008-10-09 | Xenon Pharmaceuticals Inc. | Pyrazole and pyrrole compounds useful in treating iron disorders |
| US20090069288A1 (en) | 2007-07-16 | 2009-03-12 | Breinlinger Eric C | Novel therapeutic compounds |
| JP2011511756A (ja) | 2007-08-02 | 2011-04-14 | ナームローゼ・フエンノートチヤツプ・オルガノン | Ｔｒｐｖ１モジュレータとしての５−フェニル−イソオキサゾール−３−カルボキサミド誘導体 |
| EP2219646A4 (en) | 2007-12-21 | 2010-12-22 | Univ Rochester | PROCESS FOR EXTENDING THE LIFE OF EUKARYOTIC ORGANISMS |
| WO2011151361A1 (en) | 2010-06-03 | 2011-12-08 | Glaxo Group Limited | Novel compounds |
| TW201623288A (zh) | 2014-05-14 | 2016-07-01 | 諾華公司 | 甲醯胺衍生物 |
| US9403810B2 (en) | 2014-05-14 | 2016-08-02 | Novartis Ag | Carboxamide derivatives |
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2015
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| EP3143014B1 (en) | 2018-10-24 |
| JP2017515845A (ja) | 2017-06-15 |
| WO2015177646A1 (en) | 2015-11-26 |
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| AU2015263049A1 (en) | 2016-11-24 |
| CN106536512A (zh) | 2017-03-22 |
| SG11201609311RA (en) | 2016-12-29 |
| TW201623288A (zh) | 2016-07-01 |
| AU2015263049B2 (en) | 2017-09-28 |
| MX2016014946A (es) | 2017-02-28 |
| JP6587637B2 (ja) | 2019-10-09 |
| AR100439A1 (es) | 2016-10-05 |
| UY36123A (es) | 2016-01-08 |
| US9931319B2 (en) | 2018-04-03 |
| KR20170003667A (ko) | 2017-01-09 |
| AP2016009554A0 (en) | 2016-11-30 |
| EA201692298A1 (ru) | 2017-03-31 |
| EP3143014A1 (en) | 2017-03-22 |
| US20170000770A1 (en) | 2017-01-05 |
| CN106536512B (zh) | 2019-06-07 |
| US9403833B2 (en) | 2016-08-02 |
| US20150329549A1 (en) | 2015-11-19 |
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| Date | Code | Title | Description |
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| FZDE | Discontinued |
Effective date: 20200831 |