A series of 2-mercapto-6-phenylpyrimidine-4-carboxylic acid derivatives (7a‒c, 8a‒e, 9a‒e and 10a‒e) as novel xanthine oxidase inhibitors were designed based on molecular docking, and synthesized by a new method using ketoenol acids and thiourea as the starting materials. In vitro activity assay indicated that most of the designed compounds displayed submicromolar inhibitory potency. Specifically, compound 9b had the most potent enzyme inhibitory activity with the IC₅₀ at 0.132 μM. Steady-state enzyme kinetics indicated that 9b behaved as a mixed-type inhibitor for XO.

中文翻译：

---

设计，合成和生物评价作为强力黄嘌呤氧化酶抑制剂的2-巯基-6-苯基嘧啶-4-羧酸衍生物

以分子对接为基础，设计了一系列2-巯基-6-苯基嘧啶-4-羧酸衍生物（7a‒c，8a‒e，9a 10e和10a‒e）作为黄嘌呤氧化酶抑制剂。酮烯醇酸和硫脲为起始原料的方法。体外活性测定表明，大多数设计的化合物均表现出亚微摩尔抑制潜能。具体而言，化合物9b具有最强的酶抑制活性，IC ₅₀为0.132μM。稳态酶动力学表明9b充当XO的混合型抑制剂。