GB989568A - Piperidine derivatives - Google Patents

Abstract

The invention comprises compounds of the general formula <FORM:0989568/C2/1> (wherein Ar represents a phenyl group unsubstituted or substituted by one or more substituents selected from halogen atoms and alkyl, alkoxy, alkanesulphonyl, nitro and cyano groups, A represents a straight or branched chain C2- 6 alkylene group, A1 represents a single bond or a straight or branched chain C1- 3 alkylene group, and Y represents a hydrogen atom, an alkanoyl or hydroxyethyl group, or a carbamoyl group which may be substituted on the nitrogen atom by a group Ar, the grouping -A1-O-Y being attached to the 3- or 4-position of the piperidine nucleus) and acid addition and quaternary ammonium salts thereof, pharmaceutical preparations containing them, and their preparation by (a) reacting a compound of the formula <FORM:0989568/C2/2> with a compound of the formula Ar-O-A-X (wherein X represents the acid residue of a reactive ester), (b)-in the case of compounds in which A contains a -CH2-group attached to the nitrogen atom of the piperidine nucleus-reducing the carbonyl group of a compound of the formula <FORM:0989568/C2/3> (wherein A2 represents a straight or branched chain alkylene group containing up to five carbon atoms) to a methylene group, or (c)-in the case of compounds in which A1 represents a -C(CH3)2- group and Y represents a hydrogen atom-reacting a compound of the formula <FORM:0989568/C2/4> (wherein R represents a methyl or alkoxy group and the grouping -CO-R is in the 3- or 4-position of the piperidine nucleus) with a methyl-magnesium halide and hydrolysing the product, optionally followed in each case by (i) esterification or urethanisation of compounds in which Y represents a hydrogen atom and/or (ii) acid addition or quaternary ammonium salt formation. The alkyl, alkoxy, alkanesulphonyl and alkanoyl groups contain up to four carbon atoms. The following intermediates are prepared from the starting materials indicated in parentheses: 4 - (2,21 - hydroxyethoxyethyl)piperidine (4 - vinylpyridine and ethylene glycol, via 4 - (2 - 21 - hydroxyethoxyethyl)pyridine); 4 - (1 -hydroxyethyl) - piperidine (4 - acetylpyridine); 4 - (1 - methyl - 2 - hydroxyethyl)piperidine (4 - (1-methyl - 2 - hydroxyethyl)pyridine); 1 - (2 - phenoxypropionyl) - 4 - hydroxypiperidine (2 - phenoxypropionyl chloride and 4-hydroxypiperidine); 1 - (2 - phenoxyethyl) - 4 - ethoxycarbonylpiperidine (1 - bromo - 2 - phenoxyethane and 4-ethoxycarbonylpiperidine). The compounds of the invention are anti-tussives, analgesics, antiemetics and local anaesthetics and may be administered orally, rectally or parenterally in the form of pharmaceutical preparations (e.g. compressed tablets, pills, dispersible powders, granules, capsules, emulsions, solutions, syrups, elixirs, suppositories, and sterile aqueous or non-aqueous solutions, suspensions and emulsions) containing them in association with a carrier or coating.