以黄嘌呤氧化酶为靶点的新型非嘌呤类抗痛风及高尿酸血症药物研究进展

Recent advances in novel non-purine selective inhibitors of xanthine oxidase for the treatment of hyperuricemia and gout

黄嘌呤氧化酶(XO)催化黄嘌呤生成尿酸及次黄嘌呤生成黄嘌呤的过程,是抗高尿酸血症或痛风药物研究的关键靶点。黄嘌呤氧化酶抑制剂由于作用机制明确、疗效显著而倍受关注,研发新型XO抑制剂具有广阔的应用前景。XO的结构生物学及分子模拟技术为新一代非嘌呤类XO抑制剂的合理药物设计奠定了基础。本文综述了以黄嘌呤氧化酶为靶标的新型非嘌呤类小分子杂环化合物及天然产物来源的活性分子在抗高尿酸血症或痛风药物研究领域中的进展。

Xanthine oxidase（XO） is a complex metalloflavoprotein that catalyzes the oxidation of hypoxan- thine to xanthine and uric acid, which has been recognized as one of the promising targets for treatment of hyperuricemia and gout. However, drugs available for the treatment of gout patients with hyperuricemia are still limited. There is a need to develop other xanthine oxidase inhibitors, especially those with novel chemi- cal structure types. The known reports on X-ray crystal structures of xanthine oxidase and molecular mode- ling studies will certainly be beneficial for further structure-guided design and synthesis of novel xanthine ox- idase inhibitors with diverse chemotypes. This review describes the recent advances in the non-purine ana- logues as xanthine oxidase inhibitors, including an in-depth knowledge of synthesized small molecular heterocycles and natural products with their therapeutic use.