ES2477583T3 - Compuestos de carboxamida y su uso como inhibidores de calpaína IV - Google Patents
Compuestos de carboxamida y su uso como inhibidores de calpaína IV Download PDFInfo
- Publication number
- ES2477583T3 ES2477583T3 ES10798323.1T ES10798323T ES2477583T3 ES 2477583 T3 ES2477583 T3 ES 2477583T3 ES 10798323 T ES10798323 T ES 10798323T ES 2477583 T3 ES2477583 T3 ES 2477583T3
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- Prior art keywords
- phenyl
- alkyl
- dioxo
- pyrazol
- pyridin
- Prior art date
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- -1 Carboxamide compounds Chemical class 0.000 title claims abstract description 2815
- 108010079785 calpain inhibitors Proteins 0.000 title description 28
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 96
- 125000001424 substituent group Chemical group 0.000 claims abstract description 72
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 69
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 66
- 125000003118 aryl group Chemical group 0.000 claims abstract description 64
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 59
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 51
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 39
- 150000002367 halogens Chemical class 0.000 claims abstract description 39
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 35
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 23
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 16
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims abstract description 13
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 12
- 125000000000 cycloalkoxy group Chemical group 0.000 claims abstract description 9
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims abstract description 6
- 125000004737 (C1-C6) haloalkoxy group Chemical group 0.000 claims abstract description 6
- 125000006771 (C1-C6) haloalkylthio group Chemical group 0.000 claims abstract description 5
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims abstract description 3
- 125000005865 C2-C10alkynyl group Chemical group 0.000 claims abstract description 3
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract 8
- 150000003254 radicals Chemical class 0.000 claims description 121
- 125000006317 cyclopropyl amino group Chemical group 0.000 claims description 67
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 42
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 36
- 238000011282 treatment Methods 0.000 claims description 35
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 32
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 31
- 229910052757 nitrogen Inorganic materials 0.000 claims description 30
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 28
- 150000003839 salts Chemical class 0.000 claims description 25
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 claims description 24
- 208000035475 disorder Diseases 0.000 claims description 24
- 125000003545 alkoxy group Chemical group 0.000 claims description 23
- 239000000651 prodrug Substances 0.000 claims description 23
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- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 22
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 20
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 20
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 20
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 19
- DFPAKSUCGFBDDF-UHFFFAOYSA-N Nicotinamide Chemical compound NC(=O)C1=CC=CN=C1 DFPAKSUCGFBDDF-UHFFFAOYSA-N 0.000 claims description 19
- 150000004677 hydrates Chemical class 0.000 claims description 19
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 19
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 18
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 16
- 125000005842 heteroatom Chemical group 0.000 claims description 16
- 229910052717 sulfur Inorganic materials 0.000 claims description 15
- 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 13
- 239000001257 hydrogen Substances 0.000 claims description 13
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 12
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- 239000011570 nicotinamide Substances 0.000 claims description 10
- 230000006378 damage Effects 0.000 claims description 9
- 125000006514 pyridin-2-ylmethyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 9
- 125000000586 2-(4-morpholinyl)ethoxy group Chemical group [H]C([H])(O*)C([H])([H])N1C([H])([H])C([H])([H])OC([H])([H])C1([H])[H] 0.000 claims description 8
- DHMQDGOQFOQNFH-UHFFFAOYSA-M Aminoacetate Chemical compound NCC([O-])=O DHMQDGOQFOQNFH-UHFFFAOYSA-M 0.000 claims description 8
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 125000004414 alkyl thio group Chemical group 0.000 claims description 8
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- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 8
- 125000000623 heterocyclic group Chemical group 0.000 claims description 8
- 125000000437 thiazol-2-yl group Chemical group [H]C1=C([H])N=C(*)S1 0.000 claims description 8
- 125000003342 alkenyl group Chemical group 0.000 claims description 7
- 125000000304 alkynyl group Chemical group 0.000 claims description 7
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- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 7
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- VLSSILIYHTYHQV-BPGUCPLFSA-N (2r)-n-[4-(cyclopropylamino)-3,4-dioxo-1-phenylbutan-2-yl]-1-[(2-fluorophenyl)methyl]-5-oxopyrrolidine-2-carboxamide Chemical compound FC1=CC=CC=C1CN1C(=O)CC[C@@H]1C(=O)NC(C(=O)C(=O)NC1CC1)CC1=CC=CC=C1 VLSSILIYHTYHQV-BPGUCPLFSA-N 0.000 claims description 6
- JNCMHMUGTWEVOZ-UHFFFAOYSA-N F[CH]F Chemical compound F[CH]F JNCMHMUGTWEVOZ-UHFFFAOYSA-N 0.000 claims description 6
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- VUWZPRWSIVNGKG-UHFFFAOYSA-N fluoromethane Chemical compound F[CH2] VUWZPRWSIVNGKG-UHFFFAOYSA-N 0.000 claims description 5
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 4
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- 125000004981 cycloalkylmethyl group Chemical group 0.000 claims description 4
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- 201000006938 muscular dystrophy Diseases 0.000 claims description 4
- 208000031225 myocardial ischemia Diseases 0.000 claims description 4
- OWMNFLDCTWHKQI-UHFFFAOYSA-N n-[3,4-dioxo-1-phenyl-4-(2-phenylethylamino)butan-2-yl]-2-[3-(4-fluorophenyl)pyrazol-1-yl]pyridine-3-carboxamide Chemical compound C1=CC(F)=CC=C1C1=NN(C=2C(=CC=CN=2)C(=O)NC(CC=2C=CC=CC=2)C(=O)C(=O)NCCC=2C=CC=CC=2)C=C1 OWMNFLDCTWHKQI-UHFFFAOYSA-N 0.000 claims description 4
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- 208000003890 Coronary Vasospasm Diseases 0.000 claims description 3
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- 125000005018 aryl alkenyl group Chemical group 0.000 claims description 3
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- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
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- 208000002780 macular degeneration Diseases 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
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- VLSSILIYHTYHQV-LBAQZLPGSA-N (2s)-n-[4-(cyclopropylamino)-3,4-dioxo-1-phenylbutan-2-yl]-1-[(2-fluorophenyl)methyl]-5-oxopyrrolidine-2-carboxamide Chemical compound FC1=CC=CC=C1CN1C(=O)CC[C@H]1C(=O)NC(C(=O)C(=O)NC1CC1)CC1=CC=CC=C1 VLSSILIYHTYHQV-LBAQZLPGSA-N 0.000 claims description 2
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- 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
- C07D401/04—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
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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Landscapes
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US28891809P | 2009-12-22 | 2009-12-22 | |
| US288918P | 2009-12-22 | ||
| US41047610P | 2010-11-05 | 2010-11-05 | |
| US410476P | 2010-11-05 | ||
| PCT/EP2010/070420 WO2011076812A1 (en) | 2009-12-22 | 2010-12-21 | Carboxamide compounds and their use as calpain inhibitors iv |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| ES2477583T3 true ES2477583T3 (es) | 2014-07-17 |
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
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| ES10798323.1T Active ES2477583T3 (es) | 2009-12-22 | 2010-12-21 | Compuestos de carboxamida y su uso como inhibidores de calpaína IV |
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| Country | Link |
|---|---|
| US (2) | US8598211B2 (enExample) |
| EP (1) | EP2516415B1 (enExample) |
| JP (2) | JP5913125B2 (enExample) |
| CN (2) | CN105732581A (enExample) |
| AR (1) | AR079665A1 (enExample) |
| CA (1) | CA2783714A1 (enExample) |
| ES (1) | ES2477583T3 (enExample) |
| MX (1) | MX2012007322A (enExample) |
| TW (1) | TW201132632A (enExample) |
| UY (1) | UY33149A (enExample) |
| WO (1) | WO2011076812A1 (enExample) |
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| US8236798B2 (en) * | 2009-05-07 | 2012-08-07 | Abbott Gmbh & Co. Kg | Carboxamide compounds and their use as calpain inhibitors |
| US8598211B2 (en) * | 2009-12-22 | 2013-12-03 | Abbvie Inc. | Carboxamide compounds and their use as calpain inhibitors IV |
| WO2012076639A1 (en) * | 2010-12-09 | 2012-06-14 | Abbott Gmbh & Co. Kg | Carboxamide compounds and their use as calpain inhibitors v |
| MX2014011998A (es) * | 2012-04-03 | 2015-05-11 | Abbvie Deutschland | Compuestos carboxamida y su uso como inhibidores de calpaína v. |
| US8987461B2 (en) | 2012-12-06 | 2015-03-24 | Quanticel Pharmaceuticals, Inc. | Histone demethylase inhibitors |
| EP3426674A4 (en) | 2016-03-09 | 2019-08-14 | Blade Therapeutics, Inc. | CYCLIC KETO AMID COMPOUNDS AS CALPAIN MODULATORS AND METHOD FOR THE PRODUCTION AND USE THEREOF |
| WO2018009417A1 (en) | 2016-07-05 | 2018-01-11 | Blade Therapeutics, Inc. | Calpain modulators and therapeutic uses thereof |
| KR20190063473A (ko) | 2016-09-28 | 2019-06-07 | 블레이드 테라퓨틱스, 인크. | 칼페인 조정자 및 그 치료학적 용도 |
| JP2025507472A (ja) * | 2022-03-01 | 2025-03-21 | ウエストバック バイオファーマ カンパニー リミテッド | ケトアミド系誘導体及びその製薬における使用 |
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| US4826835A (en) | 1985-10-23 | 1989-05-02 | Rorer Pharmaceutical Corporation | Pyridyl-pyridazinone and pyridyl-pyrazolinone compounds and their use in the treatment of congestive heart failure |
| US4743608A (en) | 1986-07-15 | 1988-05-10 | Rorer Pharmaceutical Corporation | Pyridone-pyridyl-imidazolyl and triazolyl compounds and their use as cardiotonic agents |
| DE19642591A1 (de) | 1996-10-15 | 1998-04-16 | Basf Ag | Neue Piperidin-Ketocarbonsäure-Derivate, deren Herstellung und Anwendung |
| DE19650975A1 (de) | 1996-12-09 | 1998-06-10 | Basf Ag | Neue heterocyclisch substituierte Benzamide und deren Anwendung |
| EP0944582B1 (de) | 1996-12-11 | 2003-07-02 | Abbott GmbH & Co. KG | Ketobenzamide als calpain-inhibitoren |
| US6083944A (en) | 1997-10-07 | 2000-07-04 | Cephalon, Inc. | Quinoline-containing α-ketoamide cysteine and serine protease inhibitors |
| CN1306505A (zh) | 1998-04-20 | 2001-08-01 | Basf公司 | 新的取代酰胺、其制备以及应用 |
| HUP0101839A3 (en) | 1998-04-20 | 2002-01-28 | Basf Ag | Heterocyclically substituted amides with cysteine protease-inhibiting effect, use of them for producing pharmaceutical compositions and pharmaceutical compositions containing them |
| JP4621351B2 (ja) * | 1998-04-20 | 2011-01-26 | アボット ゲゼルシャフト ミット ベシュレンクテル ハフツング ウント コンパニー コマンディトゲゼルシャフト | カルパインインヒビターとしての複素環式的に置換されたアミド |
| DE19817459A1 (de) * | 1998-04-20 | 1999-10-21 | Basf Ag | Neue heterozyklische substituierte Amide, Herstellung und Anwendung |
| DE19818614A1 (de) | 1998-04-20 | 1999-10-21 | Basf Ag | Neue substituierte Amide, deren Herstellung und Anwendung |
| ATE344794T1 (de) * | 1998-05-25 | 2006-11-15 | Abbott Gmbh & Co Kg | Heterocyclische substituierte amide, deren herstellung und verwendung |
| DE10114762A1 (de) | 2001-03-26 | 2002-10-02 | Knoll Gmbh | Verwendung von Cysteinprotease-Inhibitoren |
| CN101277950B (zh) | 2005-08-02 | 2013-03-27 | 弗特克斯药品有限公司 | 丝氨酸蛋白酶抑制剂 |
| PT2439205E (pt) * | 2006-12-29 | 2015-07-16 | Abbvie Deutschland | Compostos de carboxamida e seus usos como inibidores de calpaína |
| JP2010519339A (ja) | 2007-02-26 | 2010-06-03 | アキリオン ファーマシューティカルズ，インコーポレーテッド | Ｈｃｖ複製阻害剤として有用な三級アミン置換ペプチド |
| TWI453019B (zh) * | 2007-12-28 | 2014-09-21 | Abbvie Deutschland | 甲醯胺化合物 |
| US8598211B2 (en) * | 2009-12-22 | 2013-12-03 | Abbvie Inc. | Carboxamide compounds and their use as calpain inhibitors IV |
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Also Published As
| Publication number | Publication date |
|---|---|
| UY33149A (es) | 2011-06-30 |
| JP5913125B2 (ja) | 2016-04-27 |
| CN105732581A (zh) | 2016-07-06 |
| AR079665A1 (es) | 2012-02-08 |
| EP2516415A1 (en) | 2012-10-31 |
| CN102753541A (zh) | 2012-10-24 |
| US20110152325A1 (en) | 2011-06-23 |
| JP2013515040A (ja) | 2013-05-02 |
| US20140179702A1 (en) | 2014-06-26 |
| EP2516415B1 (en) | 2014-04-09 |
| JP2016065071A (ja) | 2016-04-28 |
| WO2011076812A1 (en) | 2011-06-30 |
| MX2012007322A (es) | 2012-11-06 |
| CA2783714A1 (en) | 2011-06-30 |
| TW201132632A (en) | 2011-10-01 |
| US8598211B2 (en) | 2013-12-03 |
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