RU2458055C2 - Производные бензимидазола в лечении расстройств, ассоциированных с ванилоидным рецептором trpv1 - Google Patents

Info

Publication number

RU2458055C2

RU2458055C2 RU2009103675/04A RU2009103675A RU2458055C2 RU 2458055 C2 RU2458055 C2 RU 2458055C2 RU 2009103675/04 A RU2009103675/04 A RU 2009103675/04A RU 2009103675 A RU2009103675 A RU 2009103675A RU 2458055 C2 RU2458055 C2 RU 2458055C2

Authority

RU

Russia

Prior art keywords

benzimidazol

cyano

acetamide

ethyl

methylethyl

Prior art date

2006-08-11

Links

• Espacenet
• Global Dossier
• Discuss

• 229940058303 antinematodal benzimidazole derivative Drugs 0.000 title abstract 2
• 125000003785 benzimidazolyl group Chemical class N1=C(NC2=C1C=CC=C2)* 0.000 title abstract 2
• 102000011040 TRPV Cation Channels Human genes 0.000 title 1
• 108010062740 TRPV Cation Channels Proteins 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims abstract description 192
• 150000003839 salts Chemical class 0.000 claims abstract description 128
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims abstract description 37
• 230000001684 chronic effect Effects 0.000 claims abstract description 25
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims abstract description 18
• 208000000491 Tendinopathy Diseases 0.000 claims abstract description 17
• 206010043255 Tendonitis Diseases 0.000 claims abstract description 17
• 208000002551 irritable bowel syndrome Diseases 0.000 claims abstract description 17
• 201000004415 tendinitis Diseases 0.000 claims abstract description 17
• 208000021302 gastroesophageal reflux disease Diseases 0.000 claims abstract description 16
• 229910052799 carbon Inorganic materials 0.000 claims abstract description 15
• 150000001721 carbon Chemical group 0.000 claims abstract description 14
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 13
• 208000000450 Pelvic Pain Diseases 0.000 claims abstract description 11
• 229910052736 halogen Inorganic materials 0.000 claims abstract description 11
• 150000002367 halogens Chemical class 0.000 claims abstract description 11
• 208000033808 peripheral neuropathy Diseases 0.000 claims abstract description 11
• 201000008482 osteoarthritis Diseases 0.000 claims abstract description 10
• 206010020853 Hypertonic bladder Diseases 0.000 claims abstract description 8
• 208000009722 Overactive Urinary Bladder Diseases 0.000 claims abstract description 8
• 208000020629 overactive bladder Diseases 0.000 claims abstract description 8
• -1 6-chloro-7-fluoro-1H-benzimidazol-1-yl Chemical group 0.000 claims description 83
• 238000000034 method Methods 0.000 claims description 79
• 238000011282 treatment Methods 0.000 claims description 32
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 24
• 102100029613 Transient receptor potential cation channel subfamily V member 1 Human genes 0.000 claims description 23
• 108050004388 Transient receptor potential cation channel subfamily V member 1 Proteins 0.000 claims description 23
• 208000035475 disorder Diseases 0.000 claims description 23
• NKJAPDVSHONLBX-ZDUSSCGKSA-N 2-(7-chloro-6-fluorobenzimidazol-1-yl)-n-[(1s)-1-[4-(2-cyanopropan-2-yl)phenyl]ethyl]acetamide Chemical compound C1([C@@H](NC(=O)CN2C3=C(Cl)C(F)=CC=C3N=C2)C)=CC=C(C(C)(C)C#N)C=C1 NKJAPDVSHONLBX-ZDUSSCGKSA-N 0.000 claims description 22
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 21
• 208000001294 Nociceptive Pain Diseases 0.000 claims description 19
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 13
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 11
• 206010036376 Postherpetic Neuralgia Diseases 0.000 claims description 11
• 125000006582 (C5-C6) heterocycloalkyl group Chemical group 0.000 claims description 9
• 241000124008 Mammalia Species 0.000 claims description 8
• 239000003937 drug carrier Substances 0.000 claims description 7
• 230000002401 inhibitory effect Effects 0.000 claims description 5
• AAHBXZFWPVEASC-UHFFFAOYSA-N n-[1-[4-(2-cyanopropan-2-yl)-2-methylphenyl]ethyl]-2-(7-fluorobenzimidazol-1-yl)acetamide Chemical compound C1=NC2=CC=CC(F)=C2N1CC(=O)NC(C)C1=CC=C(C(C)(C)C#N)C=C1C AAHBXZFWPVEASC-UHFFFAOYSA-N 0.000 claims description 5
• JQEQXMUAJAWHFH-UHFFFAOYSA-N 2-(7-chlorobenzimidazol-1-yl)-n-[[4-(2-cyanopropan-2-yl)-3-fluorophenyl]methyl]acetamide Chemical compound C1=C(F)C(C(C)(C#N)C)=CC=C1CNC(=O)CN1C2=C(Cl)C=CC=C2N=C1 JQEQXMUAJAWHFH-UHFFFAOYSA-N 0.000 claims description 4
• YAOGGQLFLBUIHI-HNNXBMFYSA-N 2-(7-cyanobenzimidazol-1-yl)-n-[(1s)-1-[4-(2-cyanopropan-2-yl)phenyl]ethyl]acetamide Chemical compound C1([C@@H](NC(=O)CN2C3=C(C#N)C=CC=C3N=C2)C)=CC=C(C(C)(C)C#N)C=C1 YAOGGQLFLBUIHI-HNNXBMFYSA-N 0.000 claims description 3
• AQOZKGMSGBTFDO-UHFFFAOYSA-N 2-(7-cyanobenzimidazol-1-yl)-n-[[4-(2-cyanopropan-2-yl)-2-methylphenyl]methyl]acetamide Chemical compound CC1=CC(C(C)(C)C#N)=CC=C1CNC(=O)CN1C2=C(C#N)C=CC=C2N=C1 AQOZKGMSGBTFDO-UHFFFAOYSA-N 0.000 claims description 3
• WPCWWLZADISOFB-UHFFFAOYSA-N n-[1-[4-(3-cyanopentan-3-yl)phenyl]ethyl]-2-(6,7-difluorobenzimidazol-1-yl)acetamide Chemical compound C1=CC(C(CC)(C#N)CC)=CC=C1C(C)NC(=O)CN1C2=C(F)C(F)=CC=C2N=C1 WPCWWLZADISOFB-UHFFFAOYSA-N 0.000 claims description 3
• GBACDVPSPPFDPL-UHFFFAOYSA-N n-[[4-(2-cyanopropan-2-yl)-2-methylphenyl]methyl]-2-(6,7-difluorobenzimidazol-1-yl)acetamide Chemical compound CC1=CC(C(C)(C)C#N)=CC=C1CNC(=O)CN1C2=C(F)C(F)=CC=C2N=C1 GBACDVPSPPFDPL-UHFFFAOYSA-N 0.000 claims description 3
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• 239000000126 substance Substances 0.000 abstract description 10
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• 125000000592 heterocycloalkyl group Chemical group 0.000 abstract description 3
• 238000002560 therapeutic procedure Methods 0.000 abstract description 2
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• 238000003786 synthesis reaction Methods 0.000 description 64
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• 230000015572 biosynthetic process Effects 0.000 description 63
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• HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 46
• 230000002829 reductive effect Effects 0.000 description 42
• 238000003756 stirring Methods 0.000 description 41
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 40
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• 229910000041 hydrogen chloride Inorganic materials 0.000 description 38
• 239000012074 organic phase Substances 0.000 description 34
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 33
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• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 30
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• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 29
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• AIVDGNMSAJOGES-UHFFFAOYSA-N 2-(6,7-difluorobenzimidazol-1-yl)acetic acid Chemical compound C1=C(F)C(F)=C2N(CC(=O)O)C=NC2=C1 AIVDGNMSAJOGES-UHFFFAOYSA-N 0.000 description 15
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