Design, synthesis, and biological evaluation of 5‐(4‐(pyridin‐4‐yl)‐1 HH ‐1,2,3‐triazol‐1‐yl)benzonitrile derivatives as xanthine oxidase inhibitors

摘要

> A series of 5‐(4‐(pyridin‐4‐yl)‐1 H ‐1,2,3‐triazol‐1‐yl)benzonitrile derivatives ( 1a–p ) was designed, synthesized, and identified as xanthine oxidase inhibitors with micromolar level potencies. Among them, the most promising compounds 1j and 1k were obtained with IC ₅₀ values of 8.1 and 6.7?μ m , respectively. The Lineweaver–Burk plot revealed that compound 1k acted as a mixed‐type xanthine oxidase inhibitor. SAR analysis revealed that a carbon atom occupying the X 3 position is not as effective as a nitrogen atom, and an iso ‐pentyloxy or a cyclopentyloxy at the 2‐position of benzonitrile moiety will benefit the inhibitory potency. The basis of xanthine oxidase inhibition by 1k was rationalized by molecular modeling studies.