Patent IL-116455-A (IL)
Title: Process for the preparation of imidazole compounds, some such novel imidazoles and pharmaceutical compositions comprising 5-(4-pyridyl)-4-(4-fluorophenyl)-1-(4-piperidinyl)-imidazole or pharmaceutically acceptable salts thereof
IPC: A61Q1/00
Filed: 1995-12-19
Abstract: A process for preparing a compound of the formula R1 is 4-pyridyl, pyrimidinyl, quinolyl, isoquinolinyl, quinazolin-4-yl, 1-imidazolyl or 1-benzimidazolyl, which heteraryl ring is optionally substituted with one or two substituents each of which is independently selected from C1-4 alkyl, halogen, hydroxyl, C1-4 alkoxy, C1-4 alkylthio, C1-4 alkylsulfinyl, CH2OR12, amino, mono or di-C1-6 alkyl subsituted amino, 1613 ד' באב התשס" א - July 24, 2001 N(R10)C(O)Ra or an N-heterocyclyl ring which ring has from 5 to 7 members and optionally contains an additional heteroatom selected from oxygen, sulfur or NR15; R4 is phenyl, naphth-1-yl or naphth-2-yl, or a heteroaryl, which is optionally substituted by one or two substituents, each of which is independently selected, and which, for a 4-phenyl, 4-naphth-1-yl, 5-naphth-2-yl or 6-naphth-2-yl substituent, is halogen, cyano, nitro, C(Z)NR7R17, C(Z)OR16, (CR10R20)vCOR12, SR5, SOR5, OR12, halo-substituted C14 alkyl, C1-4 alkyl, ZC(Z)R12, NR10C(Z)R16, or (CR10R20)v NR10R20 and which, for other positions of substitution, is halogen, cyano, C(Z)NR13R14, C(Z)OR3, (CR10R20)m " COR3, S(O)mR3, OR3, halo-substituted C1-4 alkyl, C1-4 alkyl, (CR10R20)m " NR10C(Z) R3, NR10S(O)m'R8, NR10S(O)m'NR7R17, ZC(Z)R3 or (CR10R23)m" NR13R14; v is 0, or an integer having a value of 1 or 2; m is 0, or the integer 1 or 2; m' is an integer having a value of 1 or 2, m" is 0, or an integer having a value of 1 to 5; R2 is C1-C10 alkyl N3, (CR10R20)n' OR9, heterocycyl, heterocyclyl C1-10 alkyl, C1-10 alkyl, halo-subsituted C1-10 alkyl, C2-C10 alkenyl, C2-C10 alkynyl, C3-7 cycloalkyl, C3-7 cycloalkyl C2-C10 alkyl, C5-7 cycloalkenyl, C5-7 cycloalkenyl- C1-C10 - alkyl, aryl, aryl C1-C10 alkyl, heteroaryl, heteroaryl-C1-10-alkyl, (CR10R20)nOR11, (CR10R20)nS(O)mR18, (CR10R20)n NHS(O)2R18, (CR10R20)n NR13R14, (CR10R20)n NO2, (CR10R20)nCN, (CR10R20)n'SO2R18, (CR10R20)n S(O)m' NR13R14, (CR10R20)nC(Z)R11, (CR10R20)n OC(Z)R11, (CR10R20)nC(Z) OR11, (CR10R20)nC(Z)NR13R14, (CR10R20)n C(Z)NR11 OR9, (CR10R20)n NR10C(Z)R11, (CR10R20)n C(Z)NR13R14, (CR10R20)n N (OR6) C(Z)NR13 R14, (CR10R20)n N(OR6) C(Z)R11, (CR10R20)n C(=NOR6)R11, (CR10R20)nNR10 1614 ד' באב התשס" א - July 24, 2001 C(=NR19) NR13 R14, (CR10R20)nOC (Z)NR13R14, (CR10R20)n NR10C(Z)NR13 R14, (CR10R20)n NR10 C(Z)OR10, 5-(R18)-1, 2, 4-oxadiazol-3-yl or 4-(R12)-5- (R18R19) - 4, 5-dihydro-1,2,4 -oxadiazol-3-yl; wherein the aryl, arylalkyl, heteroaryl, heteroaryl alkyl, heterocyclic and heterocyclic alkyl groups may be optionally substituted; n is an integer having a value of 1 to 10; n' is 0, or an integer having a value of 1 to 10; Z is oxygen or sulfur; R4 is hydrogen, C1-6 alkyl, C3-7 cycloalkyl, aryl, aryl C1-4 alkyl, heteroaryl, heteroaryl C1-4 alkyl, heterocyclyl, or heterocyclyl C1-4 alkyl; R3 is heterocyclyl, heterocyclyl C1-10 alkyl or R8; R5 is hydrogen, C1-4 alkyl, C2-4 alkenyl, C2-4 alkynyl or NR7R17, excluding the moieties SR5 being SNR7R17 and SOR5 being SOH; R6 is hydrogen, a pharmaceutically acceptable cation, C1-10 alkyl, C3-7 cycloalkyl, aryl, aryl C1-4 alkyl, heteroaryl, heteroarylalkyl, heterocyclyl, aroyl, or C1-10 alkanoyl; R7 and R17 is each independently selected from hydrogen or C1-4 alkyl or R7 and R17 together with the nitrogen to which they are attached form a heterocyclic ring of 5 to 7 members which ring optionally contains an additional heteroatom selected from oxygen, sulfur or NR15; R8 is C1-10 alkyl, halo-substituted C1-10 alkyl, C2-10 alkenyl, C2-10 alkynyl, C3-7 cycloalkyl, C5-7 cycloalkenyl, aryl, aryl C1-10 alkyl, heteroaryl, heteroaryl C1-10 alkyl, (CR10R20)n OR11, (CR10R20)nS(O)m R18, (CR10R20)n NHS(O)2 R18, (CR10R20)n NR13R14; wherein the aryl, arylalkyl, heteroaryl, heteroaryl alkyl may be optionally substituted, R9 is hydrogen, C(Z)R11 or optionally substituted C1-10 alkyl, S(O)2R18, optionally substituted aryl or optionally substituted aryl-C1-4 alkyl; R10 and R20 is each independently selected from hydrog