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 anti-acute 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.

痛风的治疗包括抑制炎症发作和治疗高尿酸血症。为了进一步发展痛风疗法，人们发现了两个系列的先天免疫传感器和黄嘌呤氧化酶（XOD）抑制剂苯并恶唑脱氧安息香肟衍生物可改善高尿酸血症和急性痛风性关节炎。体外研究表明，大多数化合物不仅抑制XOD活性，而且阻断NOD样受体（NLRP3）炎性小体和Toll样受体4（TLR4）信号传导途径的激活。更重要的是，（E）-1-（6-甲氧基苯并[ d ]恶唑-2-基）-2-（4-甲氧基苯基）乙酮肟（5d）通过调节XOD，NLRP3和TLR4表现出抗高尿酸血症和抗急性痛风性关节炎的活性。化合物5d可用作进一步设计针对先天免疫传感器和XOD的抗痛风药的工具化合物。