Synthesis and structure-activity data of some new epibatidine analogues

The high-pressure Diels-Alder reaction of N-carbomethoxypyrroles and phenyl vinyl sulfone affords versatile intermediates for the palladium-catalyzed preparation of new epibatidine analogues. Structure-activity relationships of new epibatidine analogues are presented. High affinities of K-i = 0.81 a nd 2.6 nM for the [H-3]-cytisine rat brain nicotinic acetylcholine binding sites were found for the 5-pyrimidinyl and the 5-(2-amino)-pyrimidinyl epib atidine analogues, respectively. (C) 1998 Elsevier Science Ltd. All rights reserved.