New isoxazole derivatives with a potent and selective beta 2-adrenergic activity.
A series of 1-(3-subst-5-isoxazolyl)-2-alkylaminoethanol derivatives was synthesized and tested in order to evaluate the effectiveness of the isoxazole ring in replacing the catechol moiety of beta-adrenergic compounds. Direct binding studies and the influence on beta-receptors mediated responses in isolated guinea-pig atria and guinea-pig trachea were investigated to determine the pharmacological profile of the new derivatives. The results indicate that some derivatives with proper substitution in the isoxazole ring and in the aminoalcohol chain displayed a marked selectivity towards beta 2 tracheal receptors. In vivo studies confirmed this profile, and the derivative 1-(3-bromo-5-isoxazolyl)-2-tert.butyl aminoethanol hydrochloride was selected and further developed as a potential bronchodilatory agent.
D000319:Adrenergic beta-Antagonists / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001993:Bronchodilator Agents; D055598:Chemical Phenomena; D002621:Chemistry; D004082:Dihydroalprenolol; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D066298:In Vitro Techniques; D007555:Isoxazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D010080:Oxazoles / Q000138:chemical synthesis*; D051381:Rats; D012701:Serotonin / Q000494:pharmacology; D014132:Trachea / Q000187:drug effects / Q000378:metabolism
D000319:Adrenergic beta-Antagonists; D001993:Bronchodilator Agents; D007555:Isoxazoles; D010080:Oxazoles; D012701:Serotonin; D004082:Dihydroalprenolol; D006632:Histamine