Synthesis and structure-activity relationships of selected isomeric oxime O-ethers as anticholinergic agents.
A series of isomeric (Z)-and (E)-oxime O-beta-dimethylaminoethyl ether methylhalide derivatives was synthesized, and their (Z)-and (E)-assignments were made on the basis of chemical and spectral data. The respective (Z)-and (E)-isomers were evaluated as anticholinergic agents on the rat ileum. The antimuscarinic potencies of the respective (Z)-and (E)-isomers were compared to determine the effect upon potency of this type of geometric  isomerism. Three general structure-activity  relationships and discernible among the synthesized compounds: (a) among oxime O-ethers derived from aromatic aldehydes, the higher potency consistently resides in the isomer where the aryl substituent is (E) to the ammonium ether substituent; (B) among oxime O-ethers derived from diaryl ketones, the (Z)-and (E)-isomers are approximately equipotent; and (c) oxime O-ethers derived from diaryl ketones are the most potent of the synthesized compounds.
D000818:Animals; D004987:Ethers / Q000138:chemical synthesis* / Q000494:pharmacology; D066298:In Vitro Techniques; D008722:Methods; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010091:Oximes / Q000138:chemical synthesis* / Q000494:pharmacology; D010276:Parasympatholytics / Q000138:chemical synthesis*; D051381:Rats; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004987:Ethers; D010091:Oximes; D010276:Parasympatholytics