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含柔性萘三唑甲烷结构的尿酸转运体1(URAT1)抑制剂1是一类新型的用于痛风和高尿酸血症治疗的强效候选药物.为了进一步研究其构效关系,探究其分子结构中萘环和三唑环之间CH2连接臂上取代基的空间位阻对候选药物1的生物活性的影响,设计并合成了7个含有大位阻结构的化合物2-[(5-溴-4-取代-4H-1,2,4-三唑-3-基)硫]乙酸钠(2a~2g).所设计的化合物使用了1H NMR,13C NMR和HRMS进行了表征,并测试了它们对URAT1的体外抑制活性.结果发现,CH2连接臂上不能容忍其他取代基,因为引入取代基后活性普遍显著降低,且引入取代基后的分子的柔性越差,活性越弱.本研究的结果对URAT1抑制剂的结构设计具有重要的指导作用.
Uric Acid Transporter 1 (URAT1) Inhibitor 1 Containing Flexible Naphthotriazole Methane Structure is a Novel Class of Novel Potential Drugs for the Treatment of Gout and Hyperuricemia. In order to further investigate its structure-activity relationship, explore its molecular structure The effect of the steric hindrance of the substituents on the CH2 linker between the naphthalene ring and the triazole ring on the bioactivity of Candidate 1 was studied. Seven compounds containing 2 - [(5-bromo- 4H-1,2,4-triazol-3-yl) thio] acetate (2a ~ 2g). The designed compounds were characterized by 1H NMR, 13C NMR and HRMS and tested their On the inhibitory activity of URAT1 in vitro.It was found that the CH2 linker can not tolerate other substituents, because the introduction of the substituent activity was generally significantly reduced, and the introduction of the substituent molecules of the poorer flexibility, the weaker the activity of the results of this study URAT1 inhibitor structural design has an important guiding role.