Synthesis of Hexahydro-2-pyrindine (=Hexahydrocyclopenta[c]pyridine) Derivatives as Conformationally Restricted Analogs of the Nicotinic Ligands Arecolone and Isoarecolone

This is the authors' abstract. We don't add key points for this paper.

Two hexahydropyrindine derivatives, 1,2,3,4,6,7-hexahydro-2-methyl-5H-cyclopenta[c]pyridin-5-one (1) and 1,2,3,4,5,6-hexahydro-2-methyl-7H-cyclopenta[c]pyridin-7-one (2), and their methiodides 14 and 26, respectively, were synthesized. They can be considered rigid analogues of the known nicotinic agonists arecolone (=1-(1,2,5,6-tetrahydro-1-methylpyridin-3-yl)ethanone) and isoarecolone (=1-(1,2,3,6-tetrahydro-1-methylpyridin-4-yl)ethanone). The affinity for the central nicotinic receptor were measured on rat cerebral cortex. Although only the methiodide 14, among the four conformationally restricted compounds, shows an appreciable affinity, the results obtained provide useful information on the molecular requirements at the interaction site of the central nicotinic receptors.