Derivatives of 1,3-disubstituted 2,4(1H,3H)-quinazolinediones as possible peripheral vasodilators or antihypertensive agents.
A series of 1,3-disubstituted 2,4(1H,3H)-quinazolinediones was prepared from the 3-substituted 2,4(1H,3H)-quinazolinediones by treatment with sodium hydride and the desired alkyl halide in xylene. These compounds showed varying degrees of vasodilation and antihypertensive activity without significant blockade of alpha-adrenergic receptors. 1-[3-(N,N-Dimethylamino)propyl]-3-[3-(4-phenyl1-piperazinyl)propyl]-2,4(1H,3H)-quinazolinedione, which was selected for further studies, was more potent than papaverine in inducing vasodilation and induced a prolonged decrease in systolic blood pressure of hypertensive rats upon oral administration.
D000818:Animals; D000959:Antihypertensive Agents / Q000138:chemical synthesis*; D004285:Dogs; D004837:Epinephrine / Q000037:antagonists & inhibitors; D005260:Female; D006973:Hypertension / Q000503:physiopathology; D066298:In Vitro Techniques; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D011799:Quinazolines / Q000138:chemical synthesis* / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D013329:Structure-Activity Relationship; D014665:Vasodilator Agents / Q000138:chemical synthesis*
D000959:Antihypertensive Agents; D011799:Quinazolines; D011942:Receptors, Adrenergic, alpha; D014665:Vasodilator Agents; D004837:Epinephrine