3D-QSAR Analysis of Naphthyltriazole (Lesinurad) Analogs as Potent Inhibitors of Urate Transporter

作者：Zhou Hai-Yan; Li Yuan-Yuan; Li Jing^*

来源：CHINESE JOURNAL OF STRUCTURAL CHEMISTRY, 2020, 39(3): 421-436.

DOI：10.14102/j.cnki.0254-5861.2011-2469

• 3D-QSAR
• Topomer CoMFA
• URAT1 inhibitors

To obtain useful information for identifying inhibitors of urate transporter 1 (URAT1), three-dimensional quantitative structure-activity relationship (3D-QSAR) analysis was conducted for a series of lesinurad analogs via Topomer comparative molecular field analysis (CoMFA). A 3D-QSAR model was established using a training set of 51 compounds and externally validated with a test set of 17 compounds. The Topomer CoMFA model obtained (q(2) = 0.976, r(2) = 0.990) was robust and satisfactory. Subsequently, seven compounds with significant URAT1 inhibitory activity were designed according to the contour maps produced by the Topomer CoMFA model.