Synthesis and evaluations of selective COX-2 inhibitory effects: Benzo[d] thiazol analogs

作者：He, Li-Ya; Zhang, Shan-Shan; Peng, Ding-Xin; Guan, Li-Ping^*; Wang, Si-Hong^*

来源：Bioorganic & Medicinal Chemistry Letters, 2020, 30(17): 127376.

DOI：10.1016/j.bmcl.2020.127376

• Benzo[d]thiazol
• Synthesis
• Anti-inflammatory
• Analgesic
• COX-2 inhibitors

A series of benzo[d]thiazole analogs were synthesized and evaluated for their anti-inflammatory and analgesic effects. Using an ear edema model, except for compounds 2k, 2m-2q and 3a, other compounds showed the anti-inflammatory effects. Among them, compounds 2c, 2d, and 2g showed the best anti-inflammatory activity (inhibition rate: 86.8%, 90.7% and 82.9%, respectively). By the acetic acid-induced abdominal writhing test, except for compounds 2e, 2l, 2m, 2o, 2p and 3a, other compounds showed the analgesic effects with inhibition rate values of 51.9-100% (2a-2r) and 68.6-100% (3a-3g). Next, compounds 2c, 2d, 2g, 3d, 3f, 3g that displayed the excellent anti-inflammatory and analgesic activities were evaluated for their inhibitory effect against ovine COX-1 and COX-2. Compounds 2c, 2d, 2g, 3d, 3f, 3g were weak inhibitors of the COX-1 isozyme but exhibited the moderate COX-2 isozyme inhibitory effects IC50 from 0.28 to 0.77 mu M and COX-2 selectivity indexes (SI: 18.6 to 7.2). This benzo[d]thiazole moiety will be proved to be of great significance for developing more potent COX-2 inhibitors.

• 单位
  浙江海洋大学; 延边大学