Synthesis and structural, conformational and pharmacological study of N-β(or γ)acyloxyalkylnortropinones

Abstract

A series of N-β(or γ)acyloxyalkylnortropinones was synthesized and studied by 1H and 13C NMR spectroscopies, and the crystal structure of N-[β-(diphenylacetyloxy)ethyl] nortropinone 1 was determined by X-ray diffraction. In CDCl 3 solution, the compounds studied display the same preferred conformation. The pyrrolidine and piperidone rings adopt a flattened N8 envelope and distorted chair conformation, puckered at N8 and flattened at C3, respectively, with the N-substituent in the axial position with respect to the piperidone ring. The ability of the title compounds to antagonize the histamine and acetylcholine-induced contraction of guinea pig ileum is also reported. An initial structure-activity relationship is proposed.