2-(Isoxazolylethenyl)phenoxypropanolamines: a new class of beta-receptor antagonists with antihypertensive activity.
The synthesis of a series of (E)-1-amino-3-[2-(2-isoxazolylethenyl)phenoxyl-2-propanols is described. These compounds were found to have beta- and alpha-adrenergic blocking properties, as well as hypotensive and antihypertensive properties. The beta-adrenoceptor antagonism of all these compounds was more pronounced than their alpha-sympatholytic and hypotensive activity. 3a was 16 times more potent than labetalol in beta-adrenergic receptor blockade and was effective in lowering blood pressure in acute trials on spontaneously hypertensive rats at a dosage of 15 mg/kg. Structure-activity considerations showed that antihypertensive potency was more sensitive to structural variations than beta-adrenoceptor antagonistic activity. However, in general, those compounds having the most potent beta-adrenoceptor blocking activity also lowered blood pressure most effectively.
D000317:Adrenergic alpha-Antagonists / Q000138:chemical synthesis; D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis*; D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D001794:Blood Pressure / Q000187:drug effects; D055598:Chemical Phenomena; D002621:Chemistry; D006339:Heart Rate / Q000187:drug effects; D007545:Isoproterenol / Q000037:antagonists & inhibitors; D007555:Isoxazoles / Q000138:chemical synthesis / Q000494:pharmacology; D008297:Male; D011412:Propanolamines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains
D000317:Adrenergic alpha-Antagonists; D000319:Adrenergic beta-Antagonists; D000959:Antihypertensive Agents; D007555:Isoxazoles; D011412:Propanolamines; C018658:((1,1-dimethylethyl)amino)-3-(2-(2-(3-methyl-5-isoxazolyl)ethenyl)phenoxy)-2-propanol; D007545:Isoproterenol