Synthesis and beta-adrenergic blocking activity of new aliphatic oxime ethers.
New beta-adrenergic blocking agents, most of which do not contain an aromatic nucleus, were synthesized. They were derived either from alkylamino-aliphatic oxime ethers or alkylamino-aliphatic ethers. Most active among these are O-[3-(tert-butylamino)-2-hydroxypropyl]acetoxime (8; trachea pA2 = 7.65) and 1-isobutoxy-3-(tert-butylamino)-2-propanol (15; trachea pA2 = 7.49), both of which displayed bronchoselectivity (beta 2/beta 1 ratio approximately 15). The role and importance of the aromatic nucleus in this class of compounds are discussed.
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis*; D000818:Animals; D004987:Ethers / Q000138:chemical synthesis / Q000494:pharmacology; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D010091:Oximes / Q000138:chemical synthesis* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D004987:Ethers; D010091:Oximes