Synthesis and structure--activity relationships of selected tricyclic oxime O-ethers as potential anticholinergic...

Selected isomeric and nonisomeric oxime O-ether derivatives of thioxanthone oxime were synthesized and evaluated for anticholinergic activity. The oxime O-ethers were prepared via O-alkylation of the oximate anion with appropriate aminoaklyl halides. Separation and isolation of the structural isomers were accomplished through dry-column chromatography. The racemic alpha-methyl isomer was resolved via formation of tartrate diastereomers, which were subsequently isolated. All synthesized compounds exhibited significant antimuscarinic activity. A comparison of the antimuscarinic activities of these compounds revealed that the racemic alpha-methyl isomer was the most potent and that the racemic beta-methyl isomer was the least potent. Structure-activity relationships among the oxime O-ether derivatives synthesized are discussed.