Arylethanolamines derived from salicylamide with alpha- and beta-adrenoceptor blocking activities. Preparation of labetalol, its enantiomers, and related salicylamides.
A series of phenethanolamines (3) based on salicylamide has been prepared and shown to possess beta-adrenergic blocking properties. When the basic nitrogen atom was substituted by some aralkyl groups, the compounds also blocked alpha-adrenoceptors. The 1-methyl-3-phenylpropyl derivative labetalol (34) is antihypertensive in animals and man, and syntheses of its four stereoisomers are described. The enantiomer 90 with the R configuration at both asymmetric centers possessed most of the beta-blocking activity but little alpha-blocking activity. That with the S configuration at the alcoholic carbon and the R configuration on the amino substituent, 89, is predominantly an alpha-adrenoceptor blocking agent.
D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis*; D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis*; D000818:Animals; D055598:Chemical Phenomena; D002621:Chemistry; D004285:Dogs; D004983:Ethanolamines / Q000138:chemical synthesis* / Q000494:pharmacology; D007741:Labetalol / Q000138:chemical synthesis*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D010646:Phentolamine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012457:Salicylamides / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; D012457:Salicylamides; D011433:Propranolol; D007741:Labetalol; D010646:Phentolamine