Himbacine analogs as muscarinic receptor antagonists--effects of tether and heterocyclic variations.
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.
Chackalamannil
Samuel
S
Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. samuel.chackalamannil@spcorp.com
Doller
Darío
D
McQuade
Robert
R
Ruperto
Vilma
V
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
D000470:Alkaloids; D005663:Furans; D006571:Heterocyclic Compounds; D018727:Muscarinic Antagonists; D009281:Naphthalenes; D010276:Parasympatholytics; D010880:Piperidines; D011976:Receptors, Muscarinic; D011994:Recombinant Proteins; C048172:himbacine