Department of Medicinal Chemistry, School of Pharmacy, Jilin University, China.
Biol Pharm Bull. 2009 Dec;32(12):1986-90. doi: 10.1248/bpb.32.1986.
A series of 4,5-diaryloxazole analogs were designed and the interaction between oxaprozin and cyclooxygenase-2 studied by the docking method to improve the biological activity and reduce the gastrointestinal side effects of oxaprozin. Finally, 3-(4-(4-fluorophenyl)-5-(4-aminosulfonyl-3-fluorophenyl)-oxazole-2-yl) propanoic acid (NC-2142), the best candidate, was selected for synthesis and bioassay based on the screening result. NC-2142 could lower the tumefaction rates of back metatarsus in rats, as well as reduce the writhing times in mice. NC-2142 produced fewer gastric lesions than oxaprozin. After the aminosulfonyl group was introduced into the benzene ring of oxaprozin, its analgesic and anti-inflammatory activities remained unchanged, and it reduced the number of gastric lesions. This provided a feasible method for further structure modification and optimization of oxaprozin.
设计了一系列 4,5-二芳基恶唑类似物，并通过对接方法研究了奥沙普秦与环氧化酶-2 的相互作用，以提高奥沙普秦的生物活性并降低其胃肠道副作用。最终，根据筛选结果选择了 3-(4-(4-氟苯基)-5-(4-氨基磺酰基-3-氟苯基)-恶唑-2-基)丙酸(NC-2142)作为最佳候选物进行合成和生物测定。NC-2142 可降低大鼠后跖肿胀率，并减少小鼠扭体次数。NC-2142 引起的胃损伤比奥沙普秦少。将氨基磺酰基引入奥沙普秦的苯环后，其镇痛和抗炎活性保持不变，同时减少了胃损伤的数量。这为进一步对奥沙普秦进行结构修饰和优化提供了一种可行的方法。
