Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Hamdard University, Hamdard Nagar, New Delhi 110062, India.
Eur J Med Chem. 2010 Nov;45(11):5113-9. doi: 10.1016/j.ejmech.2010.08.022. Epub 2010 Aug 14.
A number of 5-(4-substituted phenyl)-2-(substituted benzylsulfanyl)-4-(substituted phenyl)-6-methyl-1,4-dihydro-5-pyrimidine carboxamides (1-30) were designed and synthesized keeping in view the structural requirements as suggested in the pharmacophore model for antihypertensive activity. All the synthesized compounds were tested for antihypertensive activity by non-invasive blood pressure (NIBP) measurements (tail-cuff method) in rats. Almost all the tested compounds displayed considerable decrease in the blood pressure as compared to control. Thirteen compounds showed significant antihypertensive activity comparable to the standard drug nifedipine.
设计并合成了一系列 5-(4-取代苯基)-2-(取代苄硫基)-4-(取代苯基)-6-甲基-1,4-二氢-5-嘧啶甲酰胺(1-30),这些化合物的结构符合降压活性的药效团模型所提出的结构要求。通过非侵入性血压(尾套法)测量,对所有合成的化合物进行了降压活性测试。与对照组相比,几乎所有测试的化合物都显示出相当大的血压下降。13 种化合物表现出与标准药物硝苯地平相当的显著降压活性。