Molecular requirements of the active sites of the cholinergic receptors. XI - Synthesis and biological evaluation of isomuscarie and its isomers.
The synthesis of isomuscarine (IIc) and of its three isomers is described. Their structure were established on the basis of N.M.R. and I.R. data. Unlike the dioxolane (I), from which they are formally derived by substituting the oxygen in position 3 by a CHOH group, the isomuscarines are completely devoid of cholinergic activity. This result is explained by the impossibility of the corresponding receptor site of accepting a group larger than the ether oxygen. Interactions of the onium and C-7 methyl groups are assumed to be the driving forces for binding with the muscarinic receptor while a dipole-dipole interaction for oxygenated functions is proposed.
D000009:Abdominal Muscles / Q000187:drug effects; D000818:Animals; D001001:Anura; D055598:Chemical Phenomena; D002621:Chemistry; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D009116:Muscarine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D013055:Spectrophotometry, Infrared; D013329:Structure-Activity Relationship
D011950:Receptors, Cholinergic; D011976:Receptors, Muscarinic; D009116:Muscarine