Abstract

The synthesis of O-propynyloximes of N-methylpiperidinone, 3-tropinone, and 3-quinuclidinone, containing several pyrazole frameworks is described, together with their muscarinic receptor affinities. Compounds derived from N-methylpiperidinone or 3-tropinone and N-(4-methoxybenzyl)- or N-(2,4,6-trimethylbenzoyl)pyrazole showed moderate activity for muscarinic receptors in the rat central nervous system. A semi-empirical AM I calculation has shown that the O-[(benzoyl-pyrazolyl)propynyl]oximes of tropinone fit a previously described muscarinic pharmacophoric model, revealing structural features useful for the development of new muscarinic agents. (C) 2003 Elsevier Science Ltd. All rights reserved.