Adrenoceptor blocking agents. 2. 2-(alpha-Hydroxyarylmethyl)-3,3-dimethylaziridines, a new class of selective beta2-adrenoceptor antagonists.
Threo- and erythro-2-(alpha-hydroxybenzyl)-3,3-dimethylaziridines (1a and 1b) and threo-2-[alpha-hydroxy(2-naphthyl)methyl]- and 2-[alpha-hydroxy(3,4-dichlorobenzyl)]-3,3-dimethylaziridines (1d and 1c) have been prepared as conformationally restricted analogues of beta-adrenoceptor blocking agents like dichloroisoproterenol (DCI) and pronethalol. The aziridine analogues 1 except possibly 1c are competitive antagonists of isoproterenol-induced response on a guinea pig tracheal chain preparation and the order of potency is 1d greater than 1a greater than or equal to 1b greater than propranolol greater than 1c. Unlike propranolol, these compounds have no effect on the isoproterenol-induced response on guinea pig auricles and no significant local anesthetic and antiarrhythmic activity. The aziridine analogues 1 represent the first of a new class of selective beta2-adrenoceptor blocking agents.
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis*; D000403:Airway Resistance / Q000187:drug effects; D000779:Anesthetics, Local / Q000138:chemical synthesis; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000138:chemical synthesis; D001388:Aziridines / Q000138:chemical synthesis* / Q000494:pharmacology; D001389:Azirines / Q000138:chemical synthesis*; D001794:Blood Pressure / Q000187:drug effects; D002415:Cats; D005260:Female; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009928:Organ Specificity; D012119:Respiration / Q000187:drug effects; D014132:Trachea / Q000187:drug effects
D000319:Adrenergic beta-Antagonists; D000779:Anesthetics, Local; D000889:Anti-Arrhythmia Agents; D001388:Aziridines; D001389:Azirines; D007545:Isoproterenol