title: Himbacine analogs as muscarinic receptor antagonists--effects of tether and heterocyclic variations.
abstract: A number of analogs of the natural product himbacine were synthesized employing variations at the heterocyclic unit and the tether that links the heterocyclic unit to the tricyclic motif. Several of these analogs had M(2) affinity and M(1)/M(2) selectivity comparable to those of himbacine. The structural and stereochemical requirements of the heterocyclic unit for muscarinic binding are discussed in the light of these data.
authors.affiliation: Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. samuel.chackalamannil@spcorp.com
authors.forename: Samuel
authors.initials: S
authors.lastname: Chackalamannil
authors.forename: Darío
authors.initials: D
authors.lastname: Doller
authors.forename: Robert
authors.initials: R
authors.lastname: McQuade
authors.forename: Vilma
authors.initials: V
authors.lastname: Ruperto
mesh_terms: D000470:Alkaloids / Q000737:chemistry / Q000494:pharmacology*; D003001:Cloning, Molecular; D005663:Furans; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D018727:Muscarinic Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D009281:Naphthalenes; D010276:Parasympatholytics / Q000138:chemical synthesis* / Q000494:pharmacology; D010880:Piperidines; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
chemical_list: D000470:Alkaloids; D005663:Furans; D006571:Heterocyclic Compounds; D018727:Muscarinic Antagonists; D009281:Naphthalenes; D010276:Parasympatholytics; D010880:Piperidines; D011976:Receptors, Muscarinic; D011994:Recombinant Proteins; C048172:himbacine