Patent CA-1337418-C (CA)
Title: 4-aryl-4-piperiding (or pyrrolidine or hexahydroazepine) carbinols and heterocyclic analogs thereof
Inventor: CIGANEK ENGELBERT
IPC: A61P25/04
Filed: 1989-02-22
Granted: 1995-10-24
Abstract: An analgesic pharmaceutical compound of the following formula:                    (I) wherein (1) when m is 2 and R6 is other than H, then R1 independently is CH3, C2H5, n-C3H7, or allyl; R2 and R3 independently are H or alkyl of 1-4 carton atoms; or R1 and R2 taken together is a branched or unbranched alkylene bridge wherein the bridge is of 3 or 4 carbon atoms; or R2 and R3 taken together is a branched or unbranched alkylene bridge wherein the bridge is of 3 to 6 carbon atoms;  R4 is: (a)   (b)   1-naphthyl optionally substituted with one or two substituents, the same or different, selected from F, Cl, Br, perfluoroalkyl, alkylthio, alkoxy, phenoxy, alkyl, alkyl- or dialkylamino, said alkyl in the alkyl-containing groups being 1-12 carbon atoms.       (c)  3-pyrrolyl optionally substituted with one to three alkyl groups of 1-4 carbon atoms, (d)  2-, or 3-thienyl optionally substituted with Cl, Br, or alkyl of 1-4 carbon atoms, provided when 2-thienyl is substituted with alkyl it is other than the 5-position, or (e)  2-, or 3-benzothienyl or benzofuryl optionally substituted on the aromatic ring with Cl, Br or CF3; R5 independently is alkyl of 1-4 carbon atoms or when taken together with R6 is a branched or unbranched alkylene bridge of 3-11 carbon atoms; R6 independently is alkyl of 1-4 carbon atoms, or when taken together with R5 is a branched or unbranched alkylene bridge of 3-11 carbon atoms; R7 is H, alkyl of 1-4 carbon atoms, alkanoyl, or -CH2 phenyl; and (2)  when m is 1 or 3, or when R6 is H and m is 2;     then R1 independently is CH3, C2H5, n-C3H7, or allyl; R2 and R3 independently are H or alkyl of 1-4 carbon atoms; or R1 and R2 taken together is a branched or unbranched alkylene bridge wherein the bridge is of 3 or 4 carbon atoms; or R2 and R3 taken together is a branched or unbranched alkylene bridge where the bridge is of 3 to 6 carbon atoms; R4 is:      (a) phenyl or       where X is one or two substituents the same or different selected from F, Cl, Br, perfluoroalkyl, alkyl, alkyl- or dialkylamino, alkylthio, alkoxy or phenoxy, said alkyl in the alkyl-containing groups being of 1 to 12 carbon atoms; (b) 2-, 3-, or 4-biphenyl where either or both aromatic groups are substituted with 1 or 2 substituents, the same or differ-ent selected from F, Cl, alkyl, per-fluoroalkyl, alkoxy, aryloxy, alkylthio, arylthio, perfluoroalkoxy, perfluoro-alkylthio and dialkylamine, amino, said alkyl and alkoxy groups being of 1-12 carbon atoms and said aryl groups being of 6-12 carbon atoms; (c) 1- or 2-naphthyl optionally having one or two X substituents as defined in (a) above; (d) 2-, 3-, or 4-pyridyl, or 2-, or 3-pyrrolyl optionally substituted with one to three alkyl groups of 1-4 carbon atoms; (e) 2- or 3-thienyl optionally substituted with one substituent selected from Cl, Br, or alkyl of 1-4 carbon atoms; or (f) 2- or 3-benzothienyl or benzofuryl optionally substituted on the aromatic ring with Cl, Br, or CF3; R5 independently is alkyl of 1-4 carbon atoms, or when taken together with R6 is a branched or unbranched alkylene bridge of 3-11 carbon atoms;     R6 independently is H, alkyl of 1-4 carbon atoms, or when taken together with R5 is a branched or unbranched alkylene bridge of 3-11 carbon atoms; R7 is H, alkyl of 1-4 carbon atoms, alkanoyl, or -CH2 phenyl; or a pharmaceutically suitable salt or N-oxide thereof, provided that when R6 is H, R1 is methyl and m is 2, then R4 is other than C6H5, 2-MeOC6H4, 2,3-(MeO)2C6H3 and pharmaceutically suitable salts or N-oxides thereof.