Department of Chemistry, Faculty of Science, Zagazige University, Zagazige, Egypt.
Eur J Med Chem. 2009 Dec;44(12):4787-92. doi: 10.1016/j.ejmech.2009.07.013. Epub 2009 Jul 21.
A series of diazipine, pyrimidine, fused triazolopyrimidine and imide derivatives were newly synthesized using 4-phenyl-but-3-en-2-one 1 as a starting material and compounds 2 and 9 are intermediates. Initially the acute toxicity of the compounds was assayed via the determination of their LD(50). All the compounds were interestingly less toxic than the reference drug. The pharmacological screening showed that many of these obtained compounds have good analgesic, anticonvulsant and anti-inflammatory activities comparable to Valdecoxib, Carbamazepine and Predensilone as reference drugs. Regarding the protection against Carrageenan induced edema, five compounds were found more potent than Prednisolone. On the other hand, in searching for COX-2 inhibitor, the inhibition of plasma PGE2 for the compounds were determined and four compounds were found more potent than Prednisolone. The detailed synthesis, spectroscopic data, pharmacological screening and acute toxicity LD(50) for the synthesized compounds were reported.
一系列二氮嗪、嘧啶、稠合三唑嘧啶和酰亚胺衍生物，以 4-苯基-2-丁烯-1-酮 1 为起始原料，化合物 2 和 9 为中间体，经新合成。首先通过测定 LD(50)来评估化合物的急性毒性。所有化合物的毒性均明显低于参考药物。药理筛选表明，这些获得的化合物中有许多具有良好的镇痛、抗惊厥和抗炎活性，与伐地考昔、卡马西平和泼尼松龙等参考药物相当。在对抗角叉菜胶诱导的水肿方面，有 5 种化合物的作用比泼尼松龙更有效。另一方面，在寻找 COX-2 抑制剂时，测定了化合物对血浆 PGE2 的抑制作用，发现有 4 种化合物比泼尼松龙更有效。报道了合成化合物的详细合成、光谱数据、药理筛选和急性毒性 LD(50)。
