SYNTHESIS, STRUCTURAL, CONFORMATIONAL AND PHARMACOLOGICAL STUDY OF N-2'-ACYLOXYALKYLNORGRANATANONES

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 CDCl3 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 IC50's ranging from 2 × 10-4 to 1.81 × 10-6 M. © 1990.