QSAR in a series of muscarinic agents. Note II - Pyridine and furan derivatives.
Two sets of substantial picolyl and furfuryltrimethylammonium salts have been synthesized and their affinities (expressed as pD2) have been studied with the aim of characterizing muscarinic receptor spaces to which the ligand structural features bind. The new data were combined with those relative to a set of substituted benzyltrimethylammonium salts previously studied to formulate an overall QSAR which showed that the pD2 value is strongly dependent on hydrophobic and steric parameters of the ring substituent. Moreover, two indicator variables were considered to take into account the extra-activity associated with special structural features of the heterocyclic system and the further increase in activity associated with a "cooperative interaction" between the lipophilic binding of the substituent and a polar interaction of the ring heteroatom. The results confirm our earlier predictions and offer a model for ligand binding which gives a consistent view of the topology of the ligand attachment points on the receptor.
D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D002627:Chemistry, Physical; D005663:Furans / Q000494:pharmacology*; D066298:In Vitro Techniques; D010277:Parasympathomimetics; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D011976:Receptors, Muscarinic / Q000187:drug effects; D012995:Solubility; D013329:Structure-Activity Relationship
D005663:Furans; D010277:Parasympathomimetics; D011725:Pyridines; D011976:Receptors, Muscarinic