SUBSTITUTED PHENYL-ALKANOL DERIVATIVES THEIR PREPARATION AND COMPO SITIONS CONTAINING THEM

摘要

1359600 4 - (3 - Hydroxy - pyrrolidino or -piperidino)-phenylalkanol derivatives MERCK PATENT GmbH 10 March 1972 [25 March 1971] 11292/72 Heading C2C Novel 4 - (3 - hydroxy - pyrrolidino or -piperidino)-phenylalkanol derivatives of the general formula wherein RSP1/SP is a hydroxyl, C 1-6 alkoxy, C 3-6 cycloalkoxy, C 6-12 aryloxy, C 7-12 aralkoxy or C 1-18 acyloxy group, or a heterocycloalkoxy group with up to 6 carbon atoms which may optionally be substituted with an alkoxy group, RSP2/SP is a hydrogen atom or a C 1-6 alkyl, C 3-6 cycloalkyl, C 6-12 aryl, C 7-12 aralkyl or C 1-18 acyl group, RSP3/SP is a hydrogen atom or methyl group, RSP4/SP is a chlorine or bromine atom or a methyl group and n is 2 or 3, and acid addition and quaternary ammonium salts thereof are prepared, e.g. (a) when RSP1/SP is a hydroxyl group, RSP2/SP is a hydrogen atom and RSP3/SP is a methyl group, by catalytic hydrogenation of the corresponding 2-phenyl-allyl alcohol; (b) when RSP1/SP is a C 1-6 alkoxy group and RSP2/SP is a C 1-6 alkyl group, by reaction of the corresponding compound in which RSP1/SP is a hydroxyl group and RSP2/SP is a hydrogen atom with a C 1-6 alkyl iodide or bromide or a di-C 1-6 alkyl sulphate, (c) when RSP1/SP is a C 1-18 acyloxy group and RSP2/SP is a C 1-18 acyl group, by acylation of the corresponding compound in which RSP1/SP is a hydroxyl group and RSP2/SP is a hydrogen atom; (d) when RSP1/SP is a hydroxyl group and RSP2/SP is a hydrogen atom, by reduction of an appropriate phenylalkanal, phenylalkanoic acid or ester thereof or 4-(3-oxo-pyrrolidino or -piperidino)-phenylalkanol with lithium aluminium hydride; (e) when RSP1/SP is a hydroxyl group and RSP2/SP is a hydrogen atom, by alkaline hydrolysis of the corresponding compound in which RSP1/SP is a bromine atom; (f) when RSP1/SP is a hydroxyl group and RSP2/SP is a hydrogen atom, by reaction of an appropriate 4-hydroxy-alkylaniline with an #,#SP1/SP-dibromoalkanol; (g) when RSP1/SP is a hydroxyl group, RSP2/SP is a hydrogen atom and RSP4/SP is a chlorine atom, by diazotization of the corresponding compound in which RSP4/SP is an amino group, followed by treatment with cuprous chloride in hydrochloric acid; (h) when RSP1/SP is a hydroxyl group and RSP2/SP is a hydrogen atom, by alkaline hydrolysis of the corresponding 4-(3-bromo-pyrrolidino or -piperidino)-phenylalkanol; and (i) when RSP1/SP is a C 1-18 acyloxy group and RSP2/SP is a C 1-18 acyl group, by catalytic hydrogenation of the corresponding compound in which the heterooyclic ring contains a C-C double bond; followed optionally by salification or desalification of the product or separation of a resulting racemate into its optical antipodes. Pharmaceutical compositions having antiinflammatory activity comprise, as active ingredient, a 4-(3-hydroxy-pyrrolidino or -piperidino)-phenylalkanol derivative of the general formula above or an acid addition or quaternary ammonium salt thereof, together with an inert, physiologically acceptable carrier therefor, and may be administered parenterally, enterally or locally.