Xiaoyu Shi, Tong Zhao, Shuo Wang, Shujing Xu, Hui Liao, Shenghua Gao, Zhen Gao, Jian Zhang, Danhui Qi, Zhijiao Zhang, Fengxin Zheng, Youzhao Wang, Zhenqian Wang, Mingyu Yang, Qian Yang, Fan Yi, Jianxin Pang, Xinyong Liu, Peng Zhan
Gout and hyperuricemia are metabolic diseases characterized with high serum uric acid (SUA) levels that significantly impact human health. Lesinurad, a uricosuric agent, is limited to concurrent use with xanthine oxidase inhibitors (XOIs) in clinical practice due to its restricted efficacy and potential nephrotoxicity. Herein, extensive structural modifications of lesinurad were conducted through scaffold hopping and substituent modification strategies, affording 54 novel derivatives containing pyrimidine-fused cyclic structures...
March 14, 2024: Journal of Medicinal Chemistry