Design, synthesis, and structure-activity relationship studies of himbacine derived muscarinic receptor antagonists

Article abstract of DOI:10.1016/S0960-894X(99)00101-8

A parallel synthesis of racemic himbacine analogs was carried out by N- alkylation of various commercially available cyclic amine derivatives with the alkylating agent 4 which bears the tricyclic unit of himbacine. Several of these analogs have potency comparable to that of himbacine, albeit lacking the desired selectivity. Structure-activity relationship studies support the existence of a hydrophobic pocket in the receptor where the piperidine ring of dihydrohimbacine binds.