BENZODIAZEPINE DERIVATIVES AND PROCESS FOR THE MANUFACTURE THEREOF

摘要

The invention comprises 1, 3-dioxanes and 1, 3-dioxolanes, and their acid addition and quaternary ammonium salts, in which the carbon atom in the 2-position carries at least one carbocyclic or heterocyclic substituent (attached directly or through an alkylene or oxa-alkylene bridge and optionally substituted by one or more halogen atoms or C1-6 alkyl or alkoxy groups) or forms part of a spiro-carbocyclic ring (optionally substituted by one or more halogen atoms or C1-6 alkyl or alkoxy groups) and in which another ring carbon atom carries a piperidyl radical attached directly by one of its ring carbon atoms and optionally substituted on one or more ring carbon atoms by a halogen atom or a C1-6 alkyl or alkoxy group or on the nitrogen atom, e.g. by an alkyl, aralkyl, acyl (e.g. acetyl or diethylaminoacetyl), hydroxyalkyl or dialkylaminoalkyl group, and the preparation thereof by reacting a piperidyl-1, 2-ethanediol or -1, 3-propanediol with an aldehyde, ketone, acetal or ketal having at least one carbocyclic or heterocyclic radical attached (directly or indirectly) to the carbonyl or acetal carbon atom or with a carbocyclic ketone. When the 2-carbon atom carries only one carbocyclic or heterocyclic substituent, the remaining valency may be satisfied by a hydrogen atom or by an alkyl, alkoxyalkyl or haloalkyl group. The products are obtained in the form of one or more racemic mixtures, which may be resolved into their optically active antipodes. Reference is also made to the preparation of some of the compounds by reaction of the appropriate aldehydes or ketones with piperidylethylene oxides, to the introduction of the substituents on the nitrogen atom of the piperidyl radical by alkylation or acylation, and to quaternation with alkyl halides or benzyl chloride. Piperidylglycols used as starting mateials are prepared by catalytic hydrogenation of the corresponding pyridylglycols. Pharmaceutical compositions.-The compounds of the invention may be formulated with conventional carriers, e.g. into gels or aqueous solutions, for use in the treatment of gastrointestinal disturbances or as antispasmodic agents. Some of them may also be used as local anaesthetics, by infiltration or topical application.