Developing potent human uric acid transporter 1 (hURAT1) inhibitors

J Med Chem. 2011 Apr 28;54(8):2701-13. doi: 10.1021/jm1015022. Epub 2011 Mar 30.


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 (14)C-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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Drug Design
  • Humans
  • Kidney / metabolism
  • Magnetic Resonance Spectroscopy
  • Organic Anion Transporters / antagonists & inhibitors*
  • Organic Cation Transport Proteins / antagonists & inhibitors*
  • Xenopus


  • Organic Anion Transporters
  • Organic Cation Transport Proteins
  • SLC22A12 protein, human