Synthesis and structure-activity relationships of new muscarinic antagonists.
In an attempt to develop more selective muscarinic acetylcholine receptor (m-AcChR) antagonists, (R)-1-azabicyclo[2.2.2]oct-3-yl-thioxanthene-9-carboxylate, (R,S)-thiochromane-4-carboxylate, and (R,S)-chromane-4-carboxylate were synthesized. Evaluation of the binding affinities of these compounds to muscarinic receptors indicates that replacing the oxygen by sulfur in the xanthenyl and chromanyl moieties does not significantly change selectivity, but does reduce the affinity of 5 and enhance the affinity of 9a.
Section of Radiopharmaceutical Chemistry, George Washington University Medical Center, Washington, DC 20037.
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D000818:Animals; D001667:Binding, Competitive / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism; D004285:Dogs; D005260:Female; D066298:In Vitro Techniques; D009200:Myocardial Contraction / Q000187:drug effects; D010276:Parasympatholytics / Q000032:analysis / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011976:Receptors, Muscarinic / Q000187:drug effects; D013329:Structure-Activity Relationship
D010276:Parasympatholytics; D011976:Receptors, Muscarinic