Synthesis, stereochemical analysis, and neuromuscular blocking activity of selected E,E- and Z,Z-isomeric O-ethers of 4-androstene-3,17-dione dioximes.
A number of selected geometric oxime ethers were synthesized as potential neuromuscular blocking agents. The study consisted of the synthesis, separation, and stereochemical analysis of selected compounds followed by a preliminary pharmacological evaluation for neuromuscular blockade. Synthesis of the compounds began with the double oximination of 4-androstene-3,17-dione followed by TLC, column chromatography, and fractional crystallization as the purification methods. These procedures yielded two of the possible four isomers. Configurational assignments on the isolated pair were based on experiments using IR, UV, and NMR spectroscopy. Isomerically pure diethers were prepared by two methods: (a) O-alkylation of the stereochemically pure dioximes with the appropriate aminoalkyl halide, and (b) O-alkylation of the dioxime mixture followed by quaternization and subsequent isolation of configurationally pure salts via fractional crystallization. A preliminary pharmacological evaluation was conducted by using mice on a treadmill apparatus. Some structure--activity relationships are discussed.
D000735:Androstenedione / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D008968:Molecular Conformation; D009466:Neuromuscular Blocking Agents / Q000138:chemical synthesis*; D010091:Oximes / Q000138:chemical synthesis / Q000494:pharmacology; D013237:Stereoisomerism
D009466:Neuromuscular Blocking Agents; D010091:Oximes; D000735:Androstenedione