Havera H J, Vidrio H
J Med Chem. 1979 Dec;22(12):1548-50. doi: 10.1021/jm00198a024.
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.
通过在二甲苯中用氢化钠和所需的卤代烃处理3-取代的2,4(1H,3H)-喹唑啉二酮，制备了一系列1,3-二取代的2,4(1H,3H)-喹唑啉二酮。这些化合物表现出不同程度的血管舒张和抗高血压活性，而对α-肾上腺素能受体无明显阻断作用。被选作进一步研究的1-[3-(N,N-二甲基氨基)丙基]-3-[3-(4-苯基-1-哌嗪基)丙基]-2,4(1H,3H)-喹唑啉二酮，在诱导血管舒张方面比罂粟碱更有效，口服后可使高血压大鼠的收缩压持续下降。
