Department of Pharmaceutical Chemistry, Faculty of Pharmacy, University of Alexandria, Alexandria 21521, Egypt.
Eur J Med Chem. 2013 Apr;62:341-51. doi: 10.1016/j.ejmech.2012.12.003. Epub 2012 Dec 28.
A new series of thieno[2',3':4,5]pyrimido[1,2-b][1,2,4]triazines and thieno[2,3-d][1,2,4]triazolo[1,5-a]pyrimidines was synthesized. The newly synthesized compounds were evaluated for their anti-inflammatory and analgesic activity using diclofenac Na as a reference standard. Additionally, the ulcerogenic effects and acute toxicity (ALD50) values of the active compounds were also determined. In general, the thieno[2,3-d][1,2,4]triazolo[1,5-a]pyrimidine derivatives exhibited better biological activities than the thieno[2',3':4,5]pyrimido[1,2-b][1,2,4]triazines. Collectively, the thienotriazolopyrimidine derivatives 9, 13 and 14a were proved to display distinctive anti-inflammatory activity at the acute and subacute models as well as good analgesic profile with a delayed onset of action. Moreover, they revealed good gastrointestinal safety profile and are well tolerated by experimental animals with high safety margin (ALD50 > 0.3 g/kg).
合成了一系列噻吩并[2',3':4,5]嘧啶并[1,2-b][1,2,4]三嗪和噻吩并[2,3-d][1,2,4]三唑并[1,5-a]嘧啶类化合物。以双氯芬酸钠为参比标准，评价了新合成的化合物的抗炎和镇痛活性。此外，还测定了活性化合物的致溃疡作用和急性毒性（ALD50）值。一般来说，噻吩并[2,3-d][1,2,4]三唑并[1,5-a]嘧啶衍生物的生物活性优于噻吩并[2',3':4,5]嘧啶并[1,2-b][1,2,4]三嗪。总的来说，噻吩并三唑嘧啶衍生物 9、13 和 14a 在急性和亚急性模型中表现出独特的抗炎活性，以及良好的镇痛作用，起效时间延迟。此外，它们具有良好的胃肠道安全性，实验动物耐受良好，安全性高（ALD50>0.3 g/kg）。
