Development of benzoxazole deoxybenzoin oxime and acyloxylamine derivatives targeting innate immune sensors and xanthine oxidase for treatment of gout

作者：Huang, Jun; Zhou, Zehao; Zhou, Mengze; Miao, Mingxing; Li, Huanqiu^*; Hu, Qinghua^*

来源：Bioorganic & Medicinal Chemistry, 2018, 26(8): 1653-1664.

DOI：10.1016/j.bmc.2018.02.013

• Xanthine oxidase
• NOD-like receptor 3
• Toll-like receptor 4
• Anti-hyperuricemia
• Gout

Both the inhibition of inflammatory flares and the treatment of hyperuricemia itself are included in the management of gout. Extending our efforts to development of gout therapy, two series of benzoxazole deoxybenzoin oxime derivatives as inhibitors of innate immune sensors and xanthine oxidase (XOD) were discovered in improving hyperuricemia and acute gouty arthritis. In vitro studies revealed that most compounds not only suppressed XOD activity, but blocked activations of NOD-like receptor (NLRP3) inflammasome and Toll-like receptor 4 (TLR4) signaling pathway. More importantly, (E)-1-(6-methoxybenzo[d]oxazol-2-yl)-2-(4-methoxyphenyl)ethanone oxime (5d) exhibited anti-hyperuricemic and antiacute gouty arthritis activities through regulating XOD, NLRP3 and TLR4. Compound 5d may serve as a tool compound for further design of anti-gout drugs targeting both innate immune sensors and XOD.

• 出版日期2018-5-1
• 单位苏州大学; 中国药科大学