Synthesis, analgesic activity, and binding properties of some epibatidine analogs with a tropine skeleton

A series of epibatidine analogs and their positional isomers bearing an 8-a zabicyclo[3.2.1]octane moiety is described. Also some of their simplified a nalogs bearing a 3-piperidine moiety are reported. Their receptor binding p rofiles (5-HT1A, 5-HT1B, M-1, M-2, neuronal nicotinic receptor) and analges ic activity (hot plate, acetic acid induced writhing) have been studied. So me of the compounds, especially those containing an 8-azabicyclo[3.2.1]oct- 2-ene moiety possess high afinity for the nicotinic cholinergic receptor. T he most analgesically active compounds are also highly toxic. Optimized str uctures (PM3-MOPAC, Alchemy 2000, Tripos Inc.) of compounds 1-9 were compar ed with that of epibatidine.