Synthesis, structural, conformational and pharmacological study of N-2′-acyloxyalkylnorgranatanones

Abstract

A series of N-2′-acyloxyalkylnorgranatanones have been synthesized and studied by 1H and 13C NMR spectroscopy, and the crystal structure of N[2′(α,α-diphenylpropionyloxy)ethyl]norgranatanone 2 has been determined by X-ray diffraction. In CDCl 3 solution, these compounds can be described through an equilibrium between 2 flattened chair-chair conformers by nitrogen inversion. Piperidone ring is more flattened than the piperidine one, and a slight preference for the form with the N-substituent axial to the piperidone ring might be proposed. The title compounds are able to antagonize the histamine and acetylcholine-induced contractions of guinea pig ileum with IC 50's ranging from 2 × 10 −4 to 1.81 × 10 −6 M.