Synthesis of various geometric and enantiomeric oxime O-(alpha- and beta-methylcholinyl) ethers as potential anticholinergic agents.
Various enantiomeric and geometric oxime O-(alpha- and beta-methylcholinyl) ethers were synthesized as potential anticholinergic agents. The synthesis, separation, resolution, and structural characterization of these compounds are reported. The first step of the synthetic pathway involved an oxime formation, with subsequent O-alkylation of the respective oxime with 2-chloro-N,N-dimethylpropylamine hydrochloride. The separation of the alpha- and beta-structural isomers utilized vacuum fractional distillation and/or column chromatography, and the resolution of the enantiomers was accomplished via the formation of tartrate diastereoisomers. A preliminary pharmacological evaluation for anticholinergic activity was conducted using a rat ileum assay. Structure-activity relationships, including some stereochemical properties and antimuscarinic activity, are discussed.
D000818:Animals; D001577:Benzophenones / Q000138:chemical synthesis / Q000494:pharmacology; D004987:Ethers / Q000138:chemical synthesis / Q000494:pharmacology; D066298:In Vitro Techniques; D007536:Isomerism; D007659:Ketones / Q000138:chemical synthesis / Q000494:pharmacology; D008968:Molecular Conformation; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010091:Oximes / Q000138:chemical synthesis* / Q000494:pharmacology; D010276:Parasympatholytics / Q000138:chemical synthesis*; D010881:Piperidones / Q000138:chemical synthesis / Q000494:pharmacology; D051381:Rats; D013237:Stereoisomerism
D001577:Benzophenones; D004987:Ethers; D007659:Ketones; D010091:Oximes; D010276:Parasympatholytics; D010881:Piperidones