Document Detail

Developing potent human uric acid transporter 1 (hURAT1) inhibitors.
MedLine Citation:
PMID:  21449597     Owner:  NLM     Status:  MEDLINE    
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.
Michael F Wempe; Promsuk Jutabha; Bettina Quade; Timothy J Iwen; Morin M Frick; Ian R Ross; Peter J Rice; Naohiko Anzai; Hitoshi Endou
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-03-30
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  54     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2011 Apr 
Date Detail:
Created Date:  2011-04-21     Completed Date:  2011-07-04     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2701-13     Citation Subset:  IM    
School of Pharmacy, University of Colorado Anschutz Medical Campus, Aurora, Colorado 80045, United States.
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MeSH Terms
Drug Design
Kidney / metabolism
Magnetic Resonance Spectroscopy
Organic Anion Transporters / antagonists & inhibitors*
Organic Cation Transport Proteins / antagonists & inhibitors*
Grant Support
Reg. No./Substance:
0/Organic Anion Transporters; 0/Organic Cation Transport Proteins; 0/SLC22A12 protein, human

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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