Inclusion complexes of optically active and racemic 1,4-dihydro pyridines with cyclodextrin derivates.

摘要

Novel inclusion complexes of racemic 1,4-dihydropyridines and enantiomers thereof of the formula <CHEM> wherein R represents a phenyl group, substituted with nitro, trifluoromethyl, difluoromethoxy group or with one or two halo atoms (especially chlorine), R1 and R2, if the same, represent methyl groups and if one of them has the meaning of a 2-aminoethoxymethyl or cyano group, the other represents a methyl group, R3 and R4, if different, stand each time for a hydrogen, linear or branched C1-C6-alkyl, 2-methoxyethyl, 1-(phenylmethyl)-3-piperidinylphenyl, styryl, furyl, piperidino, 4-diphenylmethyl-1-piperazinylethyl, 5-phenyl-3-pirazolyloxy, 1-phenyl-methyl-3-pyrrolidinyl group or a group of the formula <CHEM> or, if the same, stand each time C1-C4 alkyl group, and of acid addition salts thereof with methyl- beta -cyclodextrin, hydroxy-ethyl- beta -cyclodextrin or hydroxypropyl- beta -cyclodextrin, with the exception of inclusion complexes of racemic dihydropyridines with HP- beta -CD, or, in case of amlodipine and enantiomeric nicardipine, also with beta -cyclodextrin, are disclosed. Whilst inclusion complexes of racemic dihydropyridines with the cited cyclodextrins are prepared in a well-known manner disclosed in the literature, enantiomerically pure dihydropyridines and inclusion complexes thereof with cyclodextrins are prepared in a novel way by means of preparative column chromatography. The invention also relates to a pharmaceutical formulation containing novel inclusion complexes and to the use thereof as calcium antagonists for the treatment of hypertension, angina pectoris and cerebrovascular disorders.