Bioisosteric replacement strategy for the synthesis of 1-azacyclic compounds with high affinity for the central nicotinic cholinergic receptors Original Research Article

Bioisosteric replacement of the isoxazole heterocycle in (3-methyl-5-isoxazolyl)methylene-azacyclic compounds with pyridine, oxadiazole, or an acyl group resulted in ligands with high to moderate affinity for the central nicotinic cholinergic receptors (IC50=2.0 to IC50>1000 nM) labeled by [3H]methylcarbamylcholine. Additionally, further support of an important distance parameter for high-affinity nicotinic compounds has been provided.