Levocabastine hydrochloride is a new, highly potent and specific histamine HI-receptor
antagonist without anticholinergic or antiserotonergic side effects. It is reported to
have both a fast onset and long duration of action. Indications are the treatment of
allergic conjunctivitis and allergic rhinitis.
4-Cyano-4-(4-fluorophenyl)-heptanedioic acid diethyl ester is obtained by
addition of ethyl acrylate to the anion from p-fluorophenylacetonitrile. By base
catalyzed cyclization of these diester (sodium methoxide, 60°C, xylene) is
synthesized an intermediate that after decarboethoxylation gives 1-(4-
fluorophenyl)-4-oxycyclohexanecarbonitrile. By condensation of 3-methyl-5-
phenylpiperidine-4-carboxylic acid benzyl ester and 1-(4-fluorophenyl)-4-
oxycyclohexanecarbonitrile under reductive hydrogenation conditions
(palladium-on-charcoal catalyst, 50°C, in ethanol) is prepared benzyl ester 4-
piperidinecarboxylic acid, 1-(4-cyano-4-(4-fluorophenyl)cyclohexyl)-3-methyl-
4-phenyl-, (3S-(1(cis),3α,4β))-. The benzyl protecting group is then removed
by hydrogenation method and 4-piperidinecarboxylic acid, 1-(4-cyano-4-(4-
fluorophenyl)cyclohexyl)-3-methyl-4-phenyl-, (3S-(1(cis),3α,4β))- obtained is
transformed into 4-piperidinecarboxylic acid, 1-(4-cyano-4-(4-fluorophenyl)
cyclohexyl)-3-methyl-4-phenyl-, hydrochloride, (3S-(1(cis), 3α,4β))-
(Levocabastine hydrochloride)
