JP2015522607A - プロテインキナーゼに対する阻害活性を有するイソキノリン−５−カルボキサミド誘導体 - Google Patents
プロテインキナーゼに対する阻害活性を有するイソキノリン−５−カルボキサミド誘導体 Download PDFInfo
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- JP2015522607A JP2015522607A JP2015523009A JP2015523009A JP2015522607A JP 2015522607 A JP2015522607 A JP 2015522607A JP 2015523009 A JP2015523009 A JP 2015523009A JP 2015523009 A JP2015523009 A JP 2015523009A JP 2015522607 A JP2015522607 A JP 2015522607A
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- Prior art keywords
- phenyl
- isoquinoline
- carboxamide
- trifluoromethyl
- amino
- 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.)
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- SJFXVNZZLJUPCS-UHFFFAOYSA-N isoquinoline-5-carboxamide Chemical class N1=CC=C2C(C(=O)N)=CC=CC2=C1 SJFXVNZZLJUPCS-UHFFFAOYSA-N 0.000 title claims abstract description 20
- 102000001253 Protein Kinase Human genes 0.000 title claims description 23
- 108060006633 protein kinase Proteins 0.000 title claims description 23
- 230000002401 inhibitory effect Effects 0.000 title description 14
- 150000001875 compounds Chemical class 0.000 claims abstract description 162
- -1 isomers Chemical class 0.000 claims abstract description 30
- 230000002159 abnormal effect Effects 0.000 claims abstract description 27
- 201000010099 disease Diseases 0.000 claims abstract description 19
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims abstract description 19
- 150000003839 salts Chemical class 0.000 claims abstract description 15
- 230000004663 cell proliferation Effects 0.000 claims abstract description 13
- 230000002265 prevention Effects 0.000 claims abstract description 12
- 239000012453 solvate Substances 0.000 claims abstract description 9
- 150000004677 hydrates Chemical class 0.000 claims abstract description 8
- 238000000034 method Methods 0.000 claims description 43
- 125000000217 alkyl group Chemical group 0.000 claims description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 239000001257 hydrogen Substances 0.000 claims description 21
- 125000003545 alkoxy group Chemical group 0.000 claims description 16
- 125000003118 aryl group Chemical group 0.000 claims description 15
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 15
- 230000004913 activation Effects 0.000 claims description 14
- AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 claims description 13
- 150000002431 hydrogen Chemical group 0.000 claims description 12
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 9
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- 125000001313 C5-C10 heteroaryl group Chemical group 0.000 claims description 8
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- 150000002367 halogens Chemical class 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 239000004480 active ingredient Substances 0.000 claims description 6
- 125000005843 halogen group Chemical group 0.000 claims description 6
- MMANGHIETAOBGN-UHFFFAOYSA-N 1-(tert-butylamino)-N-[2-methyl-5-[[3-(trifluoromethyl)phenyl]carbamoyl]phenyl]isoquinoline-5-carboxamide Chemical compound C(C)(C)(C)NC1=NC=CC=2C(=CC=CC12)C(=O)NC1=C(C=CC(=C1)C(NC1=CC(=CC=C1)C(F)(F)F)=O)C MMANGHIETAOBGN-UHFFFAOYSA-N 0.000 claims description 5
- DTQJPQBUPSOKAA-UHFFFAOYSA-N 1-(tert-butylamino)-N-[5-[[4-chloro-3-(trifluoromethyl)phenyl]carbamoylamino]-2-methylphenyl]isoquinoline-5-carboxamide Chemical compound CC1=C(NC(=O)C2=C3C=CN=C(NC(C)(C)C)C3=CC=C2)C=C(NC(=O)NC2=CC(=C(Cl)C=C2)C(F)(F)F)C=C1 DTQJPQBUPSOKAA-UHFFFAOYSA-N 0.000 claims description 5
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 5
- 125000001072 heteroaryl group Chemical group 0.000 claims description 5
- JETCTCUSGZDEGL-UHFFFAOYSA-N 1-amino-N-[2-methyl-5-[[3-(trifluoromethyl)benzoyl]amino]phenyl]isoquinoline-5-carboxamide Chemical compound NC1=NC=CC=2C(=CC=CC12)C(=O)NC1=C(C=CC(=C1)NC(C1=CC(=CC=C1)C(F)(F)F)=O)C JETCTCUSGZDEGL-UHFFFAOYSA-N 0.000 claims description 4
- WRXUZDBIWSRNAH-UHFFFAOYSA-N 1-amino-N-[5-[[3-(2-cyanopropan-2-yl)phenyl]carbamoyl]-2-methylphenyl]isoquinoline-5-carboxamide Chemical compound NC1=NC=CC=2C(=CC=CC12)C(=O)NC1=C(C=CC(=C1)C(NC1=CC(=CC=C1)C(C)(C)C#N)=O)C WRXUZDBIWSRNAH-UHFFFAOYSA-N 0.000 claims description 4
- WHQSMFHBQXZDSS-UHFFFAOYSA-N 1-amino-N-[6-methyl-1-[3-(trifluoromethyl)anilino]isoquinolin-5-yl]isoquinoline-5-carboxamide Chemical compound NC1=NC=CC=2C(=CC=CC12)C(=O)NC1=C2C=CN=C(C2=CC=C1C)NC1=CC(=CC=C1)C(F)(F)F WHQSMFHBQXZDSS-UHFFFAOYSA-N 0.000 claims description 4
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- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- ZIYOVHCFFWBQJR-UHFFFAOYSA-N 1-(tert-butylamino)-N-[2-methyl-5-(phenylcarbamoyl)phenyl]isoquinoline-5-carboxamide Chemical compound C(C)(C)(C)NC1=NC=CC=2C(=CC=CC12)C(=O)NC1=C(C=CC(=C1)C(NC1=CC=CC=C1)=O)C ZIYOVHCFFWBQJR-UHFFFAOYSA-N 0.000 claims description 3
- JQCWAZWCJOLFTK-UHFFFAOYSA-N 1-(tert-butylamino)-N-[5-[[2-fluoro-5-(trifluoromethyl)phenyl]carbamoylamino]-2-methylphenyl]isoquinoline-5-carboxamide Chemical compound CC1=C(NC(=O)C2=C3C=CN=C(NC(C)(C)C)C3=CC=C2)C=C(NC(=O)NC2=C(F)C=CC(=C2)C(F)(F)F)C=C1 JQCWAZWCJOLFTK-UHFFFAOYSA-N 0.000 claims description 3
- PRILLXFTJUYCIA-UHFFFAOYSA-N 1-[(5-methoxypyridin-2-yl)amino]-N-[2-methyl-5-[[3-(trifluoromethyl)phenyl]carbamoyl]phenyl]isoquinoline-5-carboxamide Chemical compound COC=1C=CC(=NC1)NC1=NC=CC=2C(=CC=CC12)C(=O)NC1=C(C=CC(=C1)C(NC1=CC(=CC=C1)C(F)(F)F)=O)C PRILLXFTJUYCIA-UHFFFAOYSA-N 0.000 claims description 3
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D217/00—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems
- C07D217/22—Heterocyclic compounds containing isoquinoline or hydrogenated isoquinoline ring systems with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the nitrogen-containing ring
-
- 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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Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
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| KR10-2012-0078904 | 2012-07-19 | ||
| KR1020120078904A KR20140011780A (ko) | 2012-07-19 | 2012-07-19 | 단백질 키나아제 저해활성을 갖는 이소퀴놀린-5-카복스아미드 유도체 |
| PCT/KR2013/006392 WO2014014270A1 (ko) | 2012-07-19 | 2013-07-17 | 단백질 키나아제 저해활성을 갖는 이소퀴놀린-5-카복스아미드 유도체 |
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| JP2015522607A true JP2015522607A (ja) | 2015-08-06 |
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| EP (1) | EP2876107A4 (enExample) |
| JP (1) | JP2015522607A (enExample) |
| KR (1) | KR20140011780A (enExample) |
| CN (1) | CN104487420A (enExample) |
| WO (1) | WO2014014270A1 (enExample) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
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| JP2021504434A (ja) * | 2017-11-30 | 2021-02-15 | ハンミ ファーム．カンパニー リミテッドＨａｎｍｉ Ｐｈａｒｍ．Ｃｏ．，Ｌｔｄ． | プロテインキナーゼに対する阻害活性を有するチエノ［３，２−ｄ］ピリミジン化合物 |
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| WO2016049774A1 (en) * | 2014-10-03 | 2016-04-07 | The Royal Institution For The Advancement Of Learning/Mcgill University | Urea and bis-urea based compounds and analogues thereof useful in the treatment of androgen receptor mediated diseases or disorders |
| SI3661515T1 (sl) | 2017-07-29 | 2022-06-30 | Lutris Pharma Ltd. | Novi BRaf inhibitorji in njihova uporaba za zadravljenje kožnih reakcij |
| US12310967B2 (en) | 2017-12-21 | 2025-05-27 | Gliapharm Sa | Compositions and methods of treatment for neurological disorders comprising motor neuron diseases |
| US12274703B2 (en) | 2017-12-21 | 2025-04-15 | Gliapharm Sa | Compositions and methods of treatment for neurological disorders comprising a dementia |
| US20210275516A1 (en) * | 2018-07-02 | 2021-09-09 | Ecole Polytechnique Federale De Lausanne (Epfl) | Lactate enhancing compounds and uses thereof |
| WO2020132378A2 (en) | 2018-12-22 | 2020-06-25 | Gliapharm Sa | Compositions and methods of treatment for neurological disorders comprising depression |
| MX2021009535A (es) | 2019-02-12 | 2022-10-10 | Lutris Pharma Ltd | Uso de composiciones tópicas de inhibidores de braf para el tratamiento de la dermatitis por radiación. |
| EP4149917B1 (en) * | 2020-05-12 | 2025-07-30 | Merck Sharp & Dohme LLC | Factor xi activation inhibitors |
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| NZ505845A (en) * | 1997-12-22 | 2003-10-31 | Bayer Ag | Inhibition of RAF kinase using aryl and heteroaryl substituted heterocyclic ureas |
| GB0005357D0 (en) * | 2000-03-06 | 2000-04-26 | Smithkline Beecham Plc | Compounds |
| WO2002100405A1 (en) * | 2001-06-11 | 2002-12-19 | Vertex Pharmaceuticals Incorporated | Isoquinoline inhibitors of p38 |
| JP2005504793A (ja) * | 2001-09-05 | 2005-02-17 | スミスクライン ビーチャム パブリック リミテッド カンパニー | Ｒａｆキナーゼ阻害剤としてのヘテロサイクルカルボキサミド誘導体 |
| US7446106B2 (en) * | 2001-09-05 | 2008-11-04 | Smithkline Beecham Plc | Pyridylfurans and pyrroles as Raf kinase inhibitors |
| WO2005105777A1 (en) | 2004-05-05 | 2005-11-10 | Pharmacia & Upjohn Company Llc | Substituted thiophene amide compounds for the treatment of inflammation |
| SE0401342D0 (sv) * | 2004-05-25 | 2004-05-25 | Astrazeneca Ab | Therapeutic compounds |
| SE0401345D0 (sv) | 2004-05-25 | 2004-05-25 | Astrazeneca Ab | Therapeutic compounds: Pyridine as scaffold |
| EP2528925B1 (en) * | 2010-01-29 | 2017-07-05 | Hanmi Science Co., Ltd. | THIENO[3,2-d]PYRIMIDINE DERIVATIVES HAVING INHIBITORY ACTIVITY ON PROTEIN KINASES |
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2012
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2013
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- 2013-07-17 EP EP13819868.4A patent/EP2876107A4/en not_active Withdrawn
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- 2013-07-17 JP JP2015523009A patent/JP2015522607A/ja not_active Withdrawn
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2021504434A (ja) * | 2017-11-30 | 2021-02-15 | ハンミ ファーム．カンパニー リミテッドＨａｎｍｉ Ｐｈａｒｍ．Ｃｏ．，Ｌｔｄ． | プロテインキナーゼに対する阻害活性を有するチエノ［３，２−ｄ］ピリミジン化合物 |
| JP7096333B2 (ja) | 2017-11-30 | 2022-07-05 | ハンミ ファーム．カンパニー リミテッド | プロテインキナーゼに対する阻害活性を有するチエノ［３，２－ｄ］ピリミジン化合物 |
| US11492357B2 (en) | 2017-11-30 | 2022-11-08 | Hanmi Pharm. Co., Ltd. | Thieno[3,2-d]pyrimidine derivative compound having inhibitory activity for protein kinase |
Also Published As
| Publication number | Publication date |
|---|---|
| WO2014014270A1 (ko) | 2014-01-23 |
| US20150191450A1 (en) | 2015-07-09 |
| US9388165B2 (en) | 2016-07-12 |
| KR20140011780A (ko) | 2014-01-29 |
| EP2876107A4 (en) | 2016-04-06 |
| CN104487420A (zh) | 2015-04-01 |
| EP2876107A1 (en) | 2015-05-27 |
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