Developing potent human uric acid transporter 1 (hURAT1) inhibitors

Michael F. Wempe, Promsuk Jutabha, Bettina Quade, Timothy J. Iwen, Morin M. Frick, Ian Ross, Peter J. Rice, Naohiko Anzai, Hitoshi Endou

Research output: Contribution to journalArticlepeer-review

54 Scopus citations


The kidneys are a vital organ in the human body. They serve several purposes including homeostatic functions such as regulating extracellular fluid volume and maintaining acid-base and electrolyte balance and are essential regarding the excretion of metabolic waste. Furthermore, the kidneys play an important role in uric acid secretion/reabsorption. Abnormalities associated with kidney transporters have been associated with various diseases, such as gout. The current study utilized Xenopus oocytes expressing human uric acid transporter 1 (hURAT1; SLC22A12) as an in vitro method to investigate novel compounds and their ability to inhibit 14C-uric acid uptake via hURAT1. We have prepared and tested a series of 2-ethyl-benzofuran compounds and probed the hURAT1 in vitro inhibitor structure-activity relationship. As compared to dimethoxy analogues, monophenols formed on the C ring showed the best in vitro inhibitory potential. Compounds with submicromolar (i.e., IC 50 < 1000 nM) inhibitors were prepared by brominating the corresponding phenols to produce compounds with potent uricosuric activity.

Original languageEnglish (US)
Pages (from-to)2701-2713
Number of pages13
JournalJournal of Medicinal Chemistry
Issue number8
StatePublished - Apr 28 2011

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Drug Discovery


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