Synthesis and beta-adrenergic blocking activity of new aliphatic and alicyclic oxime ethers.
We describe the synthesis and pharmacological properties of two new series of aliphatic and alicyclic beta-adrenergic blockers, most of them containing a cyclopropyl ring. They belong either to 2-hydroxy-3-(tert-butylamino)propyl ether A or 2-hydroxy-3-tert-(butylamino)propyl ketoxime ether B derivatives. The O-[2-hydroxy-3-(tert-butylamino)propyl] dicyclopropyl ketoxime 5 exhibited a beta-adrenergic antagonist activity comparable to that of propranolol. It was found that ketoxime ethers B generally showed higher potency than the corresponding ethers A. We confirm that the presence of an aromatic nucleus is not crucial for the beta-adrenergic activity. Structure-activity relationships among these series 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; D007202:Indicators and Reagents; D007545:Isoproterenol / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D009126:Muscle Relaxation / Q000187:drug effects; D010091:Oximes / Q000138:chemical synthesis* / Q000494:pharmacology; D011943:Receptors, Adrenergic, beta / Q000187:drug effects; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D004987:Ethers; D007202:Indicators and Reagents; D010091:Oximes; D011943:Receptors, Adrenergic, beta; D007545:Isoproterenol