New (homo)piperazinyl-alkyl (hetero)aryl-carbamate compounds are 5-hydroxytryptamine 4 receptor ligands useful for treating gastrointestinal, CNS, cardiac or urogenital disorders, pain or migraine

摘要

O-(Homo)piperazinyl-alkyl N-(hetero)aryl-carbamate compounds (I) are new. O-(Homo)piperazinyl-alkyl N-(hetero)aryl-carbamate compounds of formula (I) and their salts and optical or geometric isomers (or mixtures) are new. R1 = lower alkyl, aryl, haloalkyl or lower aralkyl; R2 = H or lower alkyl; A = aryl or heterocyclyl (both optionally substituted by a substituent other than R3); R3 = (NR6)k-CO-NR7-(CHR10)m-(CR11R16)p-(CHR12)q-NR8R9, NR6-CO-(CHR10)r-(CR11R16)s-(CHR12)t-NR8R9, NR6COR13 or (NR6)k-CONR7R13; R7-R13 = H, aryl, heteroaryl, heterocyclyl, aralkyl, heteroaralkyl, heterocycloalkyl, lower alkyl, cycloalkyl, alkoxyalkyl, alkylaminoalkyl or -alkyl-COOR17, or pairs of R7-R12 = a group completing at least one saturated or unsaturated ring (specifically cycloalkyl, cycloalkenyl or heterocyclyl), or R10 + R12 = COOR17; R13 = lower alkyl, cycloalkyl, aryl, heterocyclyl, aralkyl, heteroaralkyl, heterocycloalkyl, cycloalkylcarboxy, alkyl-COOR17, alkoxyalkyl, imidazopyridinyl-alkyl, CF3 or heteroarylthioalkyl; n = 1 or 2; k = 0 or 1; m, p, q, r, s, t = 0-2 Y = optionally branched 2-5C alkylene; J = C-R14 or N; G = C-R15 or N; R6, R16, R17 = H or lower alkyl, and R4, R5, R14, R15 = H, halo, lower alkyl, alkoxy, alkylthio, alkylsulfonyl, alkylsulfoxide, CF3, NO2, CN, COOH, alkylcarboxy or mono- or di-alkylamino, or R1 + R14, R14 + R5, R15 + R5 and/or R15 + R4 = a group completing a saturated or unsaturated ring, provided that: (1) R13 is not Me or Et, A = Ph, R2 = H, G and J = CH and R3 = NR6COR13 or (NR6)k-CONR7R13 and R6 and/or R7 = H, and (2) r, s and t are not all 0. Alkyl, cycloalkyl, aryl, aralkyl, heteroaryl, heterocyclyl, heterocycloalkyl, heteroaralkyl, alkylaminoalkyl, alkoxy, alkoxyalkyl, alkylthio or alkylcarboxy group and rings are optionally substituted. Independent claims are included for: (1) the new intermediates ethyl 3-(4-(2-(2-ethoxy-phenylcarbamoyloxy)-ethyl)-piperazin-1-yl)-benzoate and sodium 3-(4-(2-(2-ethoxy-phenylcarbamoyloxy)-ethyl)-piperazin-1-yl)-benzoate (including their salts), and (2) preparation of (I).