N-(1,3-Diaryl-3-oxopropyl)amides as a new template for xanthine oxidase inhibitors

作者：Nepali Kunal; Agarwal Amit; Sapra Sameer; Mittal Vineet; Kumar Raj^*; Banerjee Uttam C; Gupta Manish K; Satti Naresh K; Suri Om P; Dhar Kanaya L

来源：Bioorganic & Medicinal Chemistry, 2011, 19(18): 5569-5576.

DOI：10.1016/j.bmc.2011.07.039

• N-(1,3-Diaryl-3-oxopropyl)amides
• Xanthine oxidase
• Non-purine xanthine oxidase inhibitors
• Molecular docking

A series of forty two N-(1,3-diaryl-3-oxopropyl)amides were synthesized via an efficient, modified Dakin-West reaction and were evaluated for in vitro xanthine oxidase inhibitory activity for the first time. Structure-activity relationship analyses have been presented. Selected active xanthine oxidase inhibitors (3r, 3s, and 3zh) were assessed in vivo to study their anti-hyperuricemic effect in potassium oxonate induced hyperuricemic mice model. Compound 3s emerged as the most potent xanthine oxidase inhibitor (IC(50) = 2.45 mu M) as well as the most potent anti-hyperuricemic agent. The basis of significant inhibition of xanthine oxidase by 3s was rationalized by its molecular docking into catalytic site of xanthine oxidase.

• 出版日期2011-9-15