IL216792A - Fluorinated triazole amino acids, their pharmaceutical preparations and their uses - Google Patents

Info

Publication number

IL216792A

IL216792A IL216792A IL21679211A IL216792A IL 216792 A IL216792 A IL 216792A IL 216792 A IL216792 A IL 216792A IL 21679211 A IL21679211 A IL 21679211A IL 216792 A IL216792 A IL 216792A

Authority

IL

Israel

Prior art keywords

oxazole

ethyl

triazol

phenyl

carboxylic acid

Prior art date

2009-06-09

Links

• Espacenet
• Global Dossier
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• 239000008194 pharmaceutical composition Substances 0.000 title claims description 11
• JSIAIROWMJGMQZ-UHFFFAOYSA-N 2h-triazol-4-amine Chemical class NC1=CNN=N1 JSIAIROWMJGMQZ-UHFFFAOYSA-N 0.000 title description 29
• 150000001875 compounds Chemical class 0.000 claims description 183
• 150000003839 salts Chemical class 0.000 claims description 109
• -1 chloro, methyl Chemical group 0.000 claims description 65
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 52
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 44
• 201000010099 disease Diseases 0.000 claims description 33
• 239000002253 acid Substances 0.000 claims description 32
• 238000011282 treatment Methods 0.000 claims description 30
• LEZJUYTVYNRAGY-UHFFFAOYSA-N 2-[[5-(1,1-difluoroethyl)furan-2-yl]methyl]triazol-4-amine Chemical compound O1C(C(F)(F)C)=CC=C1CN1N=C(N)C=N1 LEZJUYTVYNRAGY-UHFFFAOYSA-N 0.000 claims description 25
• 229910052739 hydrogen Inorganic materials 0.000 claims description 24
• 230000001404 mediated effect Effects 0.000 claims description 24
• 208000027866 inflammatory disease Diseases 0.000 claims description 23
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 20
• 208000035475 disorder Diseases 0.000 claims description 19
• 230000002265 prevention Effects 0.000 claims description 19
• 239000001257 hydrogen Substances 0.000 claims description 16
• 239000003814 drug Substances 0.000 claims description 15
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 14
• 108091000054 Prion Proteins 0.000 claims description 14
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
• 125000001543 furan-2,5-diyl group Chemical group O1C(=CC=C1*)* 0.000 claims description 14
• 208000023504 respiratory system disease Diseases 0.000 claims description 14
• 206010027654 Allergic conditions Diseases 0.000 claims description 12
• 125000001153 fluoro group Chemical group F* 0.000 claims description 12
• 230000000414 obstructive effect Effects 0.000 claims description 12
• 208000002193 Pain Diseases 0.000 claims description 10
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 10
• OMCWOZYMSYZUTD-UHFFFAOYSA-N 2-methyl-5-(3-methylphenyl)-1,3-oxazole-4-carboxylic acid Chemical compound O1C(C)=NC(C(O)=O)=C1C1=CC=CC(C)=C1 OMCWOZYMSYZUTD-UHFFFAOYSA-N 0.000 claims description 9
• 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 9
• 238000004519 manufacturing process Methods 0.000 claims description 9
• 125000001424 substituent group Chemical group 0.000 claims description 9
• GEAPKHXZFUKEDK-UHFFFAOYSA-N 2-methyl-5-phenyl-1,3-oxazole-4-carboxylic acid Chemical compound O1C(C)=NC(C(O)=O)=C1C1=CC=CC=C1 GEAPKHXZFUKEDK-UHFFFAOYSA-N 0.000 claims description 8
• 208000012902 Nervous system disease Diseases 0.000 claims description 8
• 208000036110 Neuroinflammatory disease Diseases 0.000 claims description 8
• 208000025966 Neurological disease Diseases 0.000 claims description 8
• 102000029797 Prion Human genes 0.000 claims description 8
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
• 230000028993 immune response Effects 0.000 claims description 8
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
• 230000003959 neuroinflammation Effects 0.000 claims description 8
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 8
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 7
• 206010038997 Retroviral infections Diseases 0.000 claims description 7
• GBGZUQCVRRXBPC-UHFFFAOYSA-N 2-[[4-(1,1-difluoroethyl)-1,3-oxazol-2-yl]methyl]triazol-4-amine Chemical compound CC(F)(F)C1=COC(CN2N=C(N)C=N2)=N1 GBGZUQCVRRXBPC-UHFFFAOYSA-N 0.000 claims description 6
• 125000002541 furyl group Chemical group 0.000 claims description 6
• 125000001072 heteroaryl group Chemical group 0.000 claims description 6
• 125000002971 oxazolyl group Chemical group 0.000 claims description 6
• 125000000335 thiazolyl group Chemical group 0.000 claims description 6
• NDFZHVTZGZRQMP-UHFFFAOYSA-N 2-methyl-5-[3-(trifluoromethyl)phenyl]-1,3-oxazole-4-carboxylic acid Chemical compound O1C(C)=NC(C(O)=O)=C1C1=CC=CC(C(F)(F)F)=C1 NDFZHVTZGZRQMP-UHFFFAOYSA-N 0.000 claims description 5
• WUBHAXRXECUOML-UHFFFAOYSA-N 2-methyl-5-[3-(trifluoromethoxy)phenyl]-1,3-oxazole-4-carboxylic acid Chemical compound O1C(C)=NC(C(O)=O)=C1C1=CC=CC(OC(F)(F)F)=C1 WUBHAXRXECUOML-UHFFFAOYSA-N 0.000 claims description 4
• 229910052736 halogen Inorganic materials 0.000 claims description 4
• 150000002367 halogens Chemical class 0.000 claims description 4
• IASIHXQFMXAEAN-UHFFFAOYSA-N 5-(3-methoxyphenyl)-1,3-oxazole-4-carboxylic acid Chemical compound COC1=CC=CC(C2=C(N=CO2)C(O)=O)=C1 IASIHXQFMXAEAN-UHFFFAOYSA-N 0.000 claims description 3
• VXGVPBUIHUSJID-UHFFFAOYSA-N 5-(4-fluorophenyl)-1,3-oxazole-4-carboxylic acid Chemical compound N1=COC(C=2C=CC(F)=CC=2)=C1C(=O)O VXGVPBUIHUSJID-UHFFFAOYSA-N 0.000 claims description 3
• RUKDIKJSGDVSIF-UHFFFAOYSA-N 5-phenyl-1,3-oxazole-4-carboxylic acid Chemical compound N1=COC(C=2C=CC=CC=2)=C1C(=O)O RUKDIKJSGDVSIF-UHFFFAOYSA-N 0.000 claims description 3
• 125000003145 oxazol-4-yl group Chemical group O1C=NC(=C1)* 0.000 claims description 3
• ZHOCERQZGTWUBY-UHFFFAOYSA-N 5-(3,5-difluorophenyl)-2-methyl-1,3-oxazole-4-carboxylic acid Chemical compound O1C(C)=NC(C(O)=O)=C1C1=CC(F)=CC(F)=C1 ZHOCERQZGTWUBY-UHFFFAOYSA-N 0.000 claims description 2
• UHZDXZWJFQEEFP-UHFFFAOYSA-N 5-(3-chlorophenyl)-1,3-oxazole-4-carboxylic acid Chemical compound N1=COC(C=2C=C(Cl)C=CC=2)=C1C(=O)O UHZDXZWJFQEEFP-UHFFFAOYSA-N 0.000 claims description 2
• MOFHRDAQQJGDIT-UHFFFAOYSA-N 5-(3-chlorophenyl)-2-methyl-1,3-oxazole-4-carboxylic acid Chemical compound O1C(C)=NC(C(O)=O)=C1C1=CC=CC(Cl)=C1 MOFHRDAQQJGDIT-UHFFFAOYSA-N 0.000 claims description 2
• ZELDCUVJUJDDJZ-UHFFFAOYSA-N 5-(3-fluoro-5-methylphenyl)-2-methyl-1,3-oxazole-4-carboxylic acid Chemical compound O1C(C)=NC(C(O)=O)=C1C1=CC(C)=CC(F)=C1 ZELDCUVJUJDDJZ-UHFFFAOYSA-N 0.000 claims description 2
• JOEHGVJZMLKSEG-UHFFFAOYSA-N 5-[3-(dimethylamino)-4-fluorophenyl]-1,3-oxazole-4-carboxylic acid Chemical compound C1=C(F)C(N(C)C)=CC(C2=C(N=CO2)C(O)=O)=C1 JOEHGVJZMLKSEG-UHFFFAOYSA-N 0.000 claims description 2
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 2
• VTNMLIDXHPDHSX-UHFFFAOYSA-N n-[2-[[4-(1,1-difluoroethyl)-1,3-thiazol-2-yl]methyl]triazol-4-yl]-2-methyl-5-[3-(trifluoromethoxy)phenyl]-1,3-oxazole-4-carboxamide Chemical compound C=1C=CC(OC(F)(F)F)=CC=1C=1OC(C)=NC=1C(=O)NC(=N1)C=NN1CC1=NC(C(C)(F)F)=CS1 VTNMLIDXHPDHSX-UHFFFAOYSA-N 0.000 claims description 2
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 2
• QWENRTYMTSOGBR-UHFFFAOYSA-N 1H-1,2,3-Triazole Chemical compound C=1C=NNN=1 QWENRTYMTSOGBR-UHFFFAOYSA-N 0.000 claims 1
• NWILTWALAFDYML-UHFFFAOYSA-N n-[2-[[4-(1,1-difluoroethyl)-1,3-oxazol-2-yl]methyl]triazol-4-yl]-5-[3-(dimethylamino)-4-fluorophenyl]-2-methyl-1,3-oxazole-4-carboxamide Chemical compound C1=C(F)C(N(C)C)=CC(C2=C(N=C(C)O2)C(=O)NC2=NN(CC=3OC=C(N=3)C(C)(F)F)N=C2)=C1 NWILTWALAFDYML-UHFFFAOYSA-N 0.000 claims 1
• QPKKEHQQYRJQLD-UHFFFAOYSA-N n-[2-[[4-(1,1-difluoroethyl)-1,3-oxazol-2-yl]methyl]triazol-4-yl]-5-[3-(dimethylamino)phenyl]-1,3-oxazole-4-carboxamide Chemical compound CN(C)C1=CC=CC(C2=C(N=CO2)C(=O)NC2=NN(CC=3OC=C(N=3)C(C)(F)F)N=C2)=C1 QPKKEHQQYRJQLD-UHFFFAOYSA-N 0.000 claims 1
• VFPUUYHTNXSBGW-UHFFFAOYSA-N n-[2-[[4-(1,1-difluoroethyl)-1,3-thiazol-2-yl]methyl]triazol-4-yl]-2-ethyl-5-phenyl-1,3-oxazole-4-carboxamide Chemical compound C=1C=CC=CC=1C=1OC(CC)=NC=1C(=O)NC(=N1)C=NN1CC1=NC(C(C)(F)F)=CS1 VFPUUYHTNXSBGW-UHFFFAOYSA-N 0.000 claims 1
• GVCXEFKLMNKTGI-UHFFFAOYSA-N n-[2-[[4-(1,1-difluoroethyl)-1,3-thiazol-2-yl]methyl]triazol-4-yl]-2-methyl-5-(3-methylphenyl)-1,3-oxazole-4-carboxamide Chemical compound C=1C=CC(C)=CC=1C=1OC(C)=NC=1C(=O)NC(=N1)C=NN1CC1=NC(C(C)(F)F)=CS1 GVCXEFKLMNKTGI-UHFFFAOYSA-N 0.000 claims 1
• HBOGQDBJYLJHDJ-UHFFFAOYSA-N n-[2-[[4-(1,1-difluoroethyl)-1,3-thiazol-2-yl]methyl]triazol-4-yl]-5-(3-methylphenyl)-1,3-oxazole-4-carboxamide Chemical compound CC1=CC=CC(C2=C(N=CO2)C(=O)NC2=NN(CC=3SC=C(N=3)C(C)(F)F)N=C2)=C1 HBOGQDBJYLJHDJ-UHFFFAOYSA-N 0.000 claims 1
• JQRWNFORPSYAFK-UHFFFAOYSA-N n-[2-[[5-(1,1-difluoroethyl)furan-2-yl]methyl]triazol-4-yl]-5-(3-fluorophenyl)-1,3-oxazole-4-carboxamide Chemical compound O1C(C(F)(F)C)=CC=C1CN1N=C(NC(=O)C2=C(OC=N2)C=2C=C(F)C=CC=2)C=N1 JQRWNFORPSYAFK-UHFFFAOYSA-N 0.000 claims 1
• WZAGCRBRWXEAKY-UHFFFAOYSA-N n-[2-[[5-(1,1-difluoroethyl)furan-2-yl]methyl]triazol-4-yl]-5-[3-(dimethylamino)phenyl]-1,3-oxazole-4-carboxamide Chemical compound CN(C)C1=CC=CC(C2=C(N=CO2)C(=O)NC2=NN(CC=3OC(=CC=3)C(C)(F)F)N=C2)=C1 WZAGCRBRWXEAKY-UHFFFAOYSA-N 0.000 claims 1
• OCPHZROOYUWORP-UHFFFAOYSA-N n-[2-[[5-(1,1-difluoroethyl)furan-2-yl]methyl]triazol-4-yl]-5-phenyl-1,3-oxazole-4-carboxamide Chemical compound O1C(C(F)(F)C)=CC=C1CN1N=C(NC(=O)C2=C(OC=N2)C=2C=CC=CC=2)C=N1 OCPHZROOYUWORP-UHFFFAOYSA-N 0.000 claims 1
• 239000002904 solvent Substances 0.000 description 176
• 238000000034 method Methods 0.000 description 95
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 87
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• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 70
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