Patent EP-1394159-A1 (EP)
Inventor: DUBLANCHET ANNE-CLAUDE
IPC: C07D417/10
Filed: 2002-08-13
Abstract: Thiophene-2-carboxylic acid amide and ester derivatives (I) are new.  Thiophene-2-carboxylic acid amide and ester derivatives of formula (I) and their isomers and acid or base addition salts are new. X = O or S; Y = O, NH or N(alkyl); Ra = H, halo, 1-3C alkyl, OH or 1-3C alkoxy; Rb = H, halo or 1-3C alkyl; A = phenyl, 5-6C cycloalkyl or 5-6C cycloalkenyl; R1, R2 = H, halo, CN, NO2, haloalkyl, haloalkoxy, alkyl, alkenyl, alkynyl, OR4, NR4R5, S(O)nR4, COR4, COOR4, OCOR4, CONR4R5, NR5COR4, NR5SO2R4, T-CN, T-OR4, T-OCF3, T-NR4R5, T-S(O)nR4, T-COR4, T-COOR4, T-OCOR4, T-CONR4R5, T-NR4COR5, T-NR4SO2R5, R6 or T-R6; n = 0-2; T = 1-6C alkylene (optionally substituted (os) by =O. halo, alkoxy, OH, NH2 or mono- or dialkylamino, and optionally having one CH2 replaced by O, S, NH or N(alkyl)); R4 = H, alkyl, Ar, Cyc or Het; R5 = H or alkyl; R6 = Ar, Cyc or Het (all os by 1-5 of halo, CN, NO2, haloalkyl, haloalkoxy, alkyl, alkenyl, OR4, NR4R5, S(O)nR4, COR4, COOR4, OCOR4, CONR4R5, NR5COR4, NR5SO2R4, T-CN, T-OR4, T-OCF3, T-NR4R5, T-S(O)nR4, T-COR4, T-COOR4, T-OCOR4, T-CONR4R5, T-NR4COR5, T-NR5SO2R4, G1 or T-G1); G1 = Ar, Cyc or Het (all os by 1-5 of halo, CN, NO2, haloalkyl, haloalkoxy, alkyl, OH, alkoxy, OPh, OCH2Ph, NH2, mono- or di-alkylamino, SH, alkylthio, 1-7C acyl, alkylsulfinyl, COOH, alkoxycarbonyl, Ph or Het); R3 = R7 or U-R11; R7 = H or alkyl, or Ar, Cyc or Het (all os by 1-5 of halo, CN, NO2, haloalkyl, haloalkoxy, alkyl, OR8, NR8R9, S(O)mR8, COR8, COOR8, OCOR8, CONR8R9, NR8COR9, NR8SO2R9, V-CN, V-OR8, T-OCF3, V-NR8R9, V-S(O)mR8, V-COR8, V-COOR8, V-OCOR8, V-CONR8R9, V-NR8COR9, V-NR8SO2R9, R10 or V-R10); m = 0-2; V = 1-6C alkylene, 2-6C alkenylene or cyclopropylene, or 2-6C alkylene having one CH2 replaced by O, S, NH or N(alkyl); R8 = H, alkyl, Ar, Cyc or Het; R9 = H or alkyl; R10 = Ar, Cyc or Het; U = 1-6C alkylene; or 2-6C alkylene having one CH2 replaced by O, S, NH or N(alkyl); R11 = halo, OR12, NR12R13, S(O)pR12, COR12, COOR12, OCOR12, CONR12R13, NR12COR13 or NR13SO2R12, or R14 (os by 1 or 2 of halo, CN, NO2, haloalkyl, haloalkoxy, alkyl, alkenyl, alkynyl, OR15, NR15R16, S(O)qR15, COR15, COOR15, OCOR15, CONR15R16, NR16COR15, NR16SO2R15, W-CN, W-OR15, W-NR15R16, W-S(O)qR15, W-COR15, W-COOR15, W-OCOR15, W-CONR15R16, W-NR16COR15, W-NR16SO2R15, W-R17 or CO-W1-COOR15); R12, R15 = H, alkyl, Ar, Cyc or Het; R13, R16 = H or alkyl; R14, R17 = Ar, Cyc or Het; p, q = 0-2; W = as defined for V; W1 = 1-6C alkylene; Ar = 4-10C mono- or bi-cyclic aryl (one ring optionally being non-aromatic in the case of bicyclic systems); Cyc = optionally partially unsaturated, monocyclic or fused or bridged bicyclic 3-12C cycloalkyl; Het = saturated, unsaturated or aromatic, monocyclic or fused or bridged bicyclic 3-12 membered heterocycle, containing 1-4 of O, S and/or N heteroatoms and optionally containing 1 or 2 =O or =S groups; alkyl moieties have 1-6C and alkenyl or alkynyl moieties 2-6C unless specified otherwise; haloalkyl moieties contain 1-6 halo atoms; provided that: (1) the following compounds are excluded: 5-methyl-4-phenyl-thiophene-2-carboxylic acid and its ethyl ester, methyl 3-hydroxy-4-phenyl-thiophene-2-carboxylate, 3-methoxy-4-phenyl-thiophene-2-carboxylic acid and its methyl ester, 4-(4-methoxyphenyl)-thiophene-2-carboxylic acid and its methyl ester, 4-phenyl-thiophene-2-carboxylic acid and its methyl and ethyl esters, 4-(4-tert. butylphenyl)-thiophene-2-carboxylic acid, methyl 5-chloro-3-hydroxy-4-phenyl-thiophene-2-carboxylate, 4-(3,5-dimethylphenyl)-thiophene-2-carboxylic acid, methyl 4-((4-acetylamino)-phenyl)-thiophene-2-carboxylic acid, 4-phenyl-thiophene-2-carboxamide and its N-methyl and N,N-dimethyl derivatives, 5-methyl-4-phenyl-thiophene-2-carboxamide and its N-methyl and N,N-dimethyl derivatives, methyl 2-((4-(4-methoxyphenyl)-thiophen-2-yl)-carboxamido)-benzoate and N-(3-(trifluoromethyl)-phenyl)-4-(4-methoxyphenyl)-thiophene-2-carboxamide;  (2) if Ra = H and A = cyclopenten-1-yl substituted in the 2-position by os thienyl as R1, then Rb = H, halo or 2-3C alkyl;  (3) if R3 = Het as R7, then