Discovery of potent and orally bioavailable inhibitors of Human Uric Acid Transporter 1 (hURAT1) and binding mode prediction using homology model

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• 作者：Jianbiao Peng ; ^{pengjb@shhrp.com" class="auth_mail" title="E-mail the corresponding author} ; Qiyue Hu ; Chunyan Gu ; Bonian Liu ; Fangfang Jin ; Jijun Yuan ; Jun Feng ; Lei Zhang ; Jiong Lan ; Qing Dong ; Guoqing Cao
• 关键词：Gout ; Hyperuricemia ; URAT1 inhibitors ; URAT1 homology model ; 3D pharmacophore
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2016
• 出版时间：15 January 2016
• 年：2016
• 卷：26
• 期：2
• 页码：277-282
• 全文大小：2398 K

文摘

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 compound 41. 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).