Alegaon S G, Hirpara M B, Alagawadi K R, Hullatti K K, Kashniyal K
Department of Pharmaceutical Chemistry, KLES College of pharmacy, KLE University, Nehrunagar, Belgaum 590 010, Karnataka, India.
Bioorg Med Chem Lett. 2014 Nov 15;24(22):5324-9. doi: 10.1016/j.bmcl.2014.08.062.
A series of 1,3,4-trisubstituted pyrazole derivatives (3 a-f), (4 a-f), and (5 a-f) have been synthesized and evaluated for their cyclooxygenase (COX-1 and COX-2) inhibitory activity. The structures of newly synthesized compounds were characterized by IR, 1H NMR, and mass spectral analysis. All of the compounds showed good inhibition of COX-2 with IC50 of 1.33-17.5 μM. Among these derivatives, compound (5c) was the most potent and selective COX-2 inhibitor (IC50 = 1.33 μM), with a significant selectivity index (SI > 60). Molecular docking studies were carried out in order to predict the hypothetical binding mode of these compounds to the COX-2 isoenzyme. The result of present study suggests that pyrazole-thiadiazole hybrid could be an interesting approach for the design of new selective COX-2 inhibitory agents.
已合成了一系列1,3,4-三取代吡唑衍生物（3a - f）、（4a - f）和（5a - f），并对其环氧化酶（COX - 1和COX - 2）抑制活性进行了评估。通过红外光谱（IR）、核磁共振氢谱（1H NMR）和质谱分析对新合成化合物的结构进行了表征。所有化合物对COX - 2均表现出良好的抑制作用，IC50为1.33 - 17.5 μM。在这些衍生物中，化合物（5c）是最有效的选择性COX - 2抑制剂（IC50 = 1.33 μM），具有显著的选择性指数（SI > 60）。进行了分子对接研究，以预测这些化合物与COX - 2同工酶的假定结合模式。本研究结果表明，吡唑 - 噻二唑杂化物可能是设计新型选择性COX - 2抑制剂的一种有趣方法。
