A new series of substituted-N-(3,4-dimethoxyphenyl)-benzoxazole derivatives 13a–13p was synthesized and evaluated in vitro for their COX (I and II) inhibitory activity, in vivo anti-inflammatory and ulcerogenic potential. Compounds 13d, 13h, 13k, 13l and 13n exhibited significant COX-2 inhibitory activity and selectivity towards COX-2 over COX-1. These selected compounds were screened for their in vivo anti-inflammatory activity by carrageenan induced rat paw edema method. Among these compounds, 13d was the most promising analogs of the series with percent inhibition of 84.09 and IC₅₀ value of 0.04 µM and 1.02 µM (COX-2 and COX-1) respectively. Furthermore, ulcerogenic study was performed and tested compounds (13d, 13h, 13k, 13l) demonstrated a significant gastric tolerance than ibuprofen. Molecular docking study was also performed with resolved crystal structure of COX-2 to understand the binding mechanisms of newly synthesized inhibitors in the active site of COX-2 enzyme and the results were found to be concordant with the biological evaluation studies of the compounds. These newly synthesized inhibitors also showed acceptable pharmacokinetic profile in the in silico ADME/T analyses.

合成了一系列新的取代的N-（3,4-二甲氧基苯基）-苯并恶唑衍生物13a - 13p，并在体外评估了其对COX（I和II）的抑制活性，体内抗炎和致溃疡的潜力。与COX-1相比，化合物13d，13h，13k，13l和13n表现出显着的COX-2抑制活性和对COX-2的选择性。通过角叉菜胶诱导的大鼠爪水肿方法筛选这些选择的化合物的体内抗炎活性。在这些化合物中，13d是该系列最有希望的类似物，抑制百分比为84.09，IC ₅₀值分别为0.04 µM和1.02 µM（COX-2和COX-1）。此外，进行了致溃疡性研究，测试的化合物（13d，13h，13k，13l）显示出比布洛芬显着的胃耐受性。还通过解析COX-2的晶体结构进行了分子对接研究，以了解新合成的抑制剂在COX-2酶活性位点的结合机理，结果与该化合物的生物学评估研究相吻合。这些新合成的抑制剂在计算机上也显示出可接受的药代动力学特征 ADME / T分析。