ES2444780T3 - Compuestos de imidazol y pirazolopiridina como antagonistas del receptor CCR1 - Google Patents
Compuestos de imidazol y pirazolopiridina como antagonistas del receptor CCR1 Download PDFInfo
- Publication number
- ES2444780T3 ES2444780T3 ES10768356.7T ES10768356T ES2444780T3 ES 2444780 T3 ES2444780 T3 ES 2444780T3 ES 10768356 T ES10768356 T ES 10768356T ES 2444780 T3 ES2444780 T3 ES 2444780T3
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- Prior art keywords
- alkyl
- phenyl
- alkoxy
- cyclopropyl
- hydrogen
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- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 title description 6
- 150000005229 pyrazolopyridines Chemical class 0.000 title description 3
- 102000004500 CCR1 Receptors Human genes 0.000 title description 2
- 108010017319 CCR1 Receptors Proteins 0.000 title description 2
- 239000002464 receptor antagonist Substances 0.000 title description 2
- 229940044551 receptor antagonist Drugs 0.000 title description 2
- 150000001875 compounds Chemical class 0.000 claims abstract description 152
- -1 hydroxy, carboxyl Chemical group 0.000 claims abstract description 133
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims abstract description 75
- 239000001257 hydrogen Substances 0.000 claims abstract description 58
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 58
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 48
- 150000003839 salts Chemical class 0.000 claims abstract description 35
- 125000003118 aryl group Chemical group 0.000 claims abstract description 33
- 229910052736 halogen Inorganic materials 0.000 claims abstract description 30
- 150000002367 halogens Chemical class 0.000 claims abstract description 30
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 30
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 29
- 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims abstract description 28
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 28
- 125000002252 acyl group Chemical group 0.000 claims abstract description 27
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 26
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 24
- 125000004043 oxo group Chemical group O=* 0.000 claims abstract description 24
- 125000004093 cyano group Chemical group *C#N 0.000 claims abstract description 22
- 125000004122 cyclic group Chemical group 0.000 claims abstract description 20
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims abstract description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 19
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims abstract description 17
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 17
- 229910052702 rhenium Inorganic materials 0.000 claims abstract description 15
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims abstract description 14
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 13
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- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims abstract description 10
- 125000004442 acylamino group Chemical group 0.000 claims abstract description 10
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 10
- 229910006069 SO3H Inorganic materials 0.000 claims abstract description 9
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims abstract description 8
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims abstract description 7
- 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims abstract description 3
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims abstract description 3
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- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 20
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 16
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 15
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 15
- 206010039073 rheumatoid arthritis Diseases 0.000 claims description 14
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
- 239000008194 pharmaceutical composition Substances 0.000 claims description 11
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 10
- 125000002757 morpholinyl group Chemical group 0.000 claims description 9
- 208000037976 chronic inflammation Diseases 0.000 claims description 8
- 230000006020 chronic inflammation Effects 0.000 claims description 8
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 8
- 125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims description 8
- 239000000546 pharmaceutical excipient Substances 0.000 claims description 8
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 7
- 125000000335 thiazolyl group Chemical group 0.000 claims description 7
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 6
- 125000001246 bromo group Chemical group Br* 0.000 claims description 6
- 125000002541 furyl group Chemical group 0.000 claims description 6
- 125000001113 thiadiazolyl group Chemical group 0.000 claims description 5
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 4
- 125000001715 oxadiazolyl group Chemical group 0.000 claims description 4
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 3
- 125000003342 alkenyl group Chemical group 0.000 claims description 3
- 239000003937 drug carrier Substances 0.000 claims description 3
- 125000006642 (C1-C6) cyanoalkyl group Chemical group 0.000 claims description 2
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- 206010049567 Miller Fisher syndrome Diseases 0.000 claims description 2
- 201000004681 Psoriasis Diseases 0.000 claims description 2
- 229910006074 SO2NH2 Inorganic materials 0.000 claims description 2
- 206010067584 Type 1 diabetes mellitus Diseases 0.000 claims description 2
- 201000006704 Ulcerative Colitis Diseases 0.000 claims description 2
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 2
- 230000007815 allergy Effects 0.000 claims description 2
- 208000006673 asthma Diseases 0.000 claims description 2
- 125000004181 carboxyalkyl group Chemical group 0.000 claims description 2
- 208000020832 chronic kidney disease Diseases 0.000 claims description 2
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- 125000004966 cyanoalkyl group Chemical group 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
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- 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 2
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 2
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- 206010025135 lupus erythematosus Diseases 0.000 claims 1
- 125000000753 cycloalkyl group Chemical group 0.000 abstract description 2
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 87
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 81
- 238000000034 method Methods 0.000 description 73
- 239000000243 solution Substances 0.000 description 57
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- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
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- 239000007787 solid Substances 0.000 description 39
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 36
- 102100031172 C-C chemokine receptor type 1 Human genes 0.000 description 35
- 101710149814 C-C chemokine receptor type 1 Proteins 0.000 description 35
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- JTXOGWNTNOJMLN-UHFFFAOYSA-N 1-(4-fluorophenyl)pyrazolo[3,4-c]pyridine-4-carboxylic acid Chemical compound N1=CC=2C(C(=O)O)=CN=CC=2N1C1=CC=C(F)C=C1 JTXOGWNTNOJMLN-UHFFFAOYSA-N 0.000 description 28
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- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 25
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- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
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Classifications
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- 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
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- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
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- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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 ring carbon atoms
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- C07D417/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
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- 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
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| US25359009P | 2009-10-21 | 2009-10-21 | |
| US253590P | 2009-10-21 | ||
| PCT/US2010/053142 WO2011049917A1 (en) | 2009-10-21 | 2010-10-19 | Indazole and pyrazolopyridine compounds as ccr1 receptor antagonists |
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| ES2444780T3 true ES2444780T3 (es) | 2014-02-26 |
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| ES10768356.7T Active ES2444780T3 (es) | 2009-10-21 | 2010-10-19 | Compuestos de imidazol y pirazolopiridina como antagonistas del receptor CCR1 |
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| EP2285783B1 (en) | 2008-04-29 | 2014-05-21 | Boehringer Ingelheim International GmbH | Indazole compounds as ccr1 receptor antagonists |
| WO2009137338A1 (en) | 2008-05-06 | 2009-11-12 | Boehringer Ingelheim International Gmbh | Pyrazole compounds as ccr1 antagonists |
| KR20110060904A (ko) | 2008-09-26 | 2011-06-08 | 베링거 인겔하임 인터내셔날 게엠베하 | Ｃｃｒ1 수용체 길항제로서의 아자인다졸 화합물 |
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| EP2493875B1 (en) * | 2009-10-27 | 2014-08-06 | Boehringer Ingelheim International GmbH | Heterocyclic compounds as ccr1 receptor antagonists |
| WO2011137109A1 (en) | 2010-04-30 | 2011-11-03 | Boehringer Ingelheim International Gmbh | Azaindazole amide compounds as ccr1 receptor antagonists |
| JP5684406B2 (ja) | 2010-12-23 | 2015-03-11 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｃｃｒ１受容体アンタゴニストとしてのピラゾロピペリジン化合物 |
| CA2852160A1 (en) | 2011-10-28 | 2013-05-02 | Galderma Research & Development | New leukocyte infiltrate markers for rosacea and uses thereof |
| EP3131902B1 (en) | 2014-04-14 | 2019-06-12 | Boehringer Ingelheim International GmbH | Compounds as modulators of ror gamma |
| CN112707831A (zh) * | 2021-02-05 | 2021-04-27 | 阿里生物新材料（常州）有限公司 | 一种3-（1-氨基环丙基）苯甲酸甲酯的合成方法 |
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| KR20110060904A (ko) | 2008-09-26 | 2011-06-08 | 베링거 인겔하임 인터내셔날 게엠베하 | Ｃｃｒ1 수용체 길항제로서의 아자인다졸 화합물 |
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| WO2011137109A1 (en) | 2010-04-30 | 2011-11-03 | Boehringer Ingelheim International Gmbh | Azaindazole amide compounds as ccr1 receptor antagonists |
| JP5684406B2 (ja) | 2010-12-23 | 2015-03-11 | ベーリンガー インゲルハイム インターナショナル ゲゼルシャフト ミット ベシュレンクテル ハフツング | Ｃｃｒ１受容体アンタゴニストとしてのピラゾロピペリジン化合物 |
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- 2010-10-19 PT PT107683567T patent/PT2491028E/pt unknown
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| US20120270870A1 (en) | 2012-10-25 |
| WO2011049917A1 (en) | 2011-04-28 |
| TN2012000180A1 (en) | 2013-12-12 |
| IN2012DN03449A (OSRAM) | 2015-10-23 |
| PT2491028E (pt) | 2014-02-04 |
| PE20121433A1 (es) | 2012-11-10 |
| AU2010308277A1 (en) | 2012-04-26 |
| DK2491028T3 (da) | 2014-01-13 |
| JP5542946B2 (ja) | 2014-07-09 |
| ECSP12011904A (es) | 2012-10-30 |
| CO6531488A2 (es) | 2012-09-28 |
| IL218823A0 (en) | 2012-06-28 |
| GEP20146103B (en) | 2014-05-27 |
| CL2012000967A1 (es) | 2012-09-14 |
| KR20120087923A (ko) | 2012-08-07 |
| EA021015B1 (ru) | 2015-03-31 |
| CN102666526A (zh) | 2012-09-12 |
| US9056858B2 (en) | 2015-06-16 |
| AP2012006204A0 (en) | 2012-04-30 |
| HRP20140213T1 (hr) | 2014-04-11 |
| PL2491028T3 (pl) | 2014-05-30 |
| EP2491028B1 (en) | 2013-12-11 |
| MX2012004644A (es) | 2012-05-08 |
| SI2491028T1 (sl) | 2014-03-31 |
| PH12012500775A1 (en) | 2012-11-26 |
| JP2013508376A (ja) | 2013-03-07 |
| BR112012009331A2 (pt) | 2019-09-24 |
| MA33675B1 (fr) | 2012-10-01 |
| EA201200602A1 (ru) | 2012-12-28 |
| RS53130B (sr) | 2014-06-30 |
| CA2778060A1 (en) | 2011-04-28 |
| NZ599132A (en) | 2014-05-30 |
| EP2491028A1 (en) | 2012-08-29 |
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