Patent NZ-610312-A (NZ)
Title: 6-amino-2-phenylamino-1h-benzimidazole-5-carboxamide- derivatives and their use as microsomal prostaglandin e2 synthase-1 inhibitors
Inventor: PRIEPKE HENNING
IPC: C07D487/08
Filed: 2011-12-09
Abstract: Disclosed are 6-amino-2-phenylamino-1H-benzimidazole-5-carboxamide derivatives of formula (I) in which R1 represents halo, OH, CN, alkyl, alkynyl, alkoxy; R2 represents halo, CN, alkyl and alkoxy; R3 and R4 independently represent hydrogen, halo, CN, alkyl and alkoxy; Ra and Rb independently represent hydrogen, alkyl or both together with the carbon atom which they are bound to, form a cycloalkylene ring, or a 4-6 membered heterocycloalkylene ring; W represents C(O), S(O), S(O)2, C(O)O, C(O)NRd which groups are bound to the nitrogen of the -NH-moiety via carbon or sulfur atom; M represents alkyl, alkynyl, cycloalkyl, cycloalkylalkyl, aryl or heteroaryl; R6 represents hydrogen, alkyl, alkynyl, heterocycloalkyl, heterocycloalkylalkyl, cycloalkyl or cycloalkylalkyl; R7 and R9 independently represent hydrogen, halo, CN, alkyl, cycloalkyl, cycloalkylalkyl, alkoxy, cycloalkyloxy, and cycloalkylalkoxy; L represents amino, NHR10, NR10R11 or a heterocycloalkyl group which is bound to the benzimidazole through a nitrogen atom and which can optionally be annulated to a phenyl or a 5- or 6-membered heteroaryl ring; A represents alkyl, alkynyl, aryl, aralkyl, cycloalkyl, cycloalkylalkyl, heterocycloalkyl, heterocycloalkylalkyl, heteroaryl, and heteroarylalkyl; wherein many of the above substituents may further be optionally substituted with the remaining substituents being as defined herein. Representative compounds include N-(4-fluoro-3-chloro-phenyl)-2-{ 2,6-dichloro-3-[(2,2-dimethyl-propionylamino)-methyl]phenylamino} -6-(4-fluoro-piperidinyl)-1-methyl-1H-benzimidazole-5-carboxylic acid amide, N-(trans-4-trifluoromethyl-cyclohexyl)-2-{ 2,6-dichloro-3-[(2,2-dimethyl-propionylamino)methyl]-phenylamino} -6-[3,3-difluoro-cyclobutylamino]-1-methyl-1H-benzimidazole-5-carboxylic acid amide, N-(trans-4-trifluoromethyl-cyclohexyl)-2-{ 2,6-dichloro-3-[((1-methyl-cyclobutyl)carbonylamino)-methyl]-phenylamino} -6-[3-aza-bicyclo[3.1.0]hex-1-yl]-1-methyl-1H-benzimidazole-5-carboxylic acid amide, N-(3,3,3-trifluoropropyl)-2-{ 2,6-dichloro-3-[(tert-butoxycarbonylamino)-methyl]-phenylamino} -6-[4-trifluoromethyl-piperidin-1-yl]-1-methyl-1H-benzimidazole-5-carboxylic acid amide, N-(3-tert-butyl-isoxazol-5-yl)-2-{ 2,6-dichloro-3-[(2,2-dimethyl-propionylamino)-methyl]phenylamino-6-[4-trifluoromethyl-piperidin-1-yl]-1-methyl-1H-benzimidazole-5-carboxylic acid amide, N-(trans-4-trifluoromethyl-cyclohexyl)-2-{ 2,6-dichloro-3-[(2,2-dimethyl-propionylamino)-methyl]-phenylamino} -6-[N-methyl-N-(1,1-dioxo-tetrahydro-thiophen-3-yl)-amino]-1-methyl-1H-benzimidazole-5-carboxylic acid amide and N-(trans-4-trifluoromethyl-cyclohexyl)-2-{ 2,6-dichloro-3-[(2,2-dimethyl-propionylamino)-methyl]-phenylamino} -6-[N-methyl-N-(4-fluorobenzyl)amino]-1-methyl-1H-benzimidazole-5-carboxylic acid amide. Also disclosed is a pharmaceutical composition comprising at least one compound as defined above, or a pharmaceutically acceptable salt thereof in admixture with a pharmaceutically acceptable adjuvant, diluent and/or carrier, for the treatment and/or prevention of inflammatory diseases and/or associated conditions, in particular pain.