Design, synthesis, and structure-activity relationship studies of himbacine derived muscarinic receptor antagonists.
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.
Doller
D
D
Schering-Plough Research Institute, Kenilworth, NJ 07033, USA.
Chackalamannil
S
S
Czarniecki
M
M
McQuade
R
R
Ruperto
V
V
D000470:Alkaloids / Q000138:chemical synthesis* / Q000494:pharmacology; D005663:Furans; D007700:Kinetics; D008956:Models, Chemical; D008958:Models, Molecular; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000737:chemistry*; D009281:Naphthalenes; D010880:Piperidines; D013329:Structure-Activity Relationship
D000470:Alkaloids; D005663:Furans; D018727:Muscarinic Antagonists; D009281:Naphthalenes; D010880:Piperidines; C048172:himbacine