Monge A, Martinez-Merino V, Sanmartin C, Ochoa M C, Fernandez-Alvarez E
Centro de Investigación en Farmacobiología Aplicada (C.I.F.A.), Universidad de Navarra, Pamplona, Spain.
Arzneimittelforschung. 1990 Dec;40(12):1349-52.
New 5H-[1,3]thiazolo[3,2-a]pyrido[3,2-e]pyrimidines 1 and 6,10-dihydro-5H-pyrido[3',2':5,6]pyrimido[2,1-c] [1,2,4]triazines 4 with 5-one, 5-thione or 5-hydrazono substituents and in some cases 1,2,3,4 or 8,9 hydrogenated are synthetized. The diuretic, natriuretic and kaliuretic activities of these compounds in Wistar rats at a dose of 24 mg/kg were estimated. A series of 24 possible derivatives of 1 and 4 possessing diuretic and saliuretic activities are investigated for structure-activity relationships in light of Fujita-Ban model. The Fujita-Ban group contributions have been calculated for different structural variations on the parent ring 1a. It is observed that the hydrogenation of pyridine, [1,3]thiazole or [1,2,4]triazine rings on 1 or 4 decrease the diuretic and saliuretic activities.
合成了带有5-酮、5-硫酮或5-腙取代基且在某些情况下为1,2,3,4或8,9氢化的新型5H-[1,3]噻唑并[3,2-a]吡啶并[3,2-e]嘧啶1和6,10-二氢-5H-吡啶并[3',2':5,6]嘧啶并[2,1-c][1,2,4]三嗪4。评估了这些化合物在Wistar大鼠中剂量为24 mg/kg时的利尿、利钠和利钾活性。根据藤田-班模型，对一系列具有利尿和利钠活性的1和4的24种可能衍生物进行了构效关系研究。已针对母环1a上的不同结构变化计算了藤田-班组贡献。观察到1或4上吡啶、[1,3]噻唑或[1,2,4]三嗪环的氢化会降低利尿和利钠活性。
