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.