Discovery of potent and orally bioavailable inhibitors of Human Uric Acid Transporter 1 (hURAT1) and binding mode prediction using homology model. Issue 2 (15th January 2016)

• Record Type: Journal Article
• Authors: Peng, Jianbiao; Hu, Qiyue; Gu, Chunyan; Liu, Bonian; Jin, Fangfang; Yuan, Jijun; Feng, Jun; Zhang, Lei; Lan, Jiong; Dong, Qing; Cao, Guoqing
• Is Part Of: Bioorganic & medicinal chemistry letters. Volume 26:Issue 2(2016)
• Page Start: 277
• Page End: 282
• Publication Date: 2016-01-15
• Subjects: Gout -- Hyperuricemia -- URAT1 inhibitors -- URAT1 homology model -- 3D pharmacophore; Bioorganic chemistry -- Periodicals; Pharmaceutical chemistry -- Periodicals; 572
• DOI: 10.1016/j.bmcl.2015.12.040
• Languages: English
• ISSNs: 0960-894X

Abstract

Graphical abstract: This Letter describes the discovery of a series of potent inhibitors of Human Uric Acid Transporter 1 (hURAT1). Lead generation and optimization via 3D pharmacophore analysis resulted in compound41 . With an IC50 of 33.7 nM, 41 also demonstrated good oral bioavailability in rat (74.8%) and displayed a consistent PK profile across all species tested (rat, dog and monkey). Abstract: This Letter describes the discovery of a series of potent inhibitors of Human Uric Acid Transporter 1 (hURAT1). Lead generation and optimization via 3D pharmacophore analysis resulted in compound41 . With an IC50 of 33.7 nM, 41 also demonstrated good oral bioavailability in rat (74.8%) and displayed a consistent PK profile across all species tested (rat, dog and monkey).