Next Article in Journal
Unfolding/Refolding Study on Collagen from Sea Cucumber Based on 2D Fourier Transform Infrared Spectroscopy
Previous Article in Journal
A Green Approach for Allylations of Aldehydes and Ketones: Combining Allylborate, Mechanochemistry and Lanthanide Catalyst
Article Menu
Issue 11 (November) cover image

Export Article

Open AccessArticle
Molecules 2016, 21(11), 1543;

Discovery of a Flexible Triazolylbutanoic Acid as a Highly Potent Uric Acid Transporter 1 (URAT1) Inhibitor

School of Chemistry and Chemical Engineering, Shandong University, Jinan 250100, China
Tianjin Key Laboratory of Molecular Design and Drug Discovery, Tianjin Institute of Pharmaceutical Research, Tianjin 300193, China
Authors to whom correspondence should be addressed.
Academic Editor: Diego Muñoz-Torrero
Received: 24 October 2016 / Revised: 9 November 2016 / Accepted: 10 November 2016 / Published: 16 November 2016
(This article belongs to the Section Medicinal Chemistry)
Full-Text   |   PDF [1636 KB, uploaded 16 November 2016]   |  


In order to systematically explore and understand the structure–activity relationship (SAR) of a lesinurad-based hit (1c) derived from the replacement of the S atom in lesinurad with CH2, 18 compounds (1a1r) were designed, synthesized and subjected to in vitro URAT1 inhibitory assay. The SAR exploration led to the discovery of a highly potent flexible URAT1 inhibitor, 1q, which was 31-fold more potent than parent lesinurad (IC50 = 0.23 μM against human URAT1 for 1q vs 7.18 μM for lesinurad). The present study discovered a flexible molecular scaffold, as represented by 1q, which might serve as a promising prototype scaffold for further development of potent URAT1 inhibitors, and also demonstrated that the S atom in lesinurad was not indispensable for its URAT1 inhibitory activity. View Full-Text
Keywords: gout; hyperuricemia; URAT1 inhibitor; lesinurad; synthesis gout; hyperuricemia; URAT1 inhibitor; lesinurad; synthesis

Graphical abstract

This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited (CC BY 4.0).

Share & Cite This Article

MDPI and ACS Style

Tian, H.; Liu, W.; Zhou, Z.; Shang, Q.; Liu, Y.; Xie, Y.; Liu, C.; Xu, W.; Tang, L.; Wang, J.; Zhao, G. Discovery of a Flexible Triazolylbutanoic Acid as a Highly Potent Uric Acid Transporter 1 (URAT1) Inhibitor. Molecules 2016, 21, 1543.

Show more citation formats Show less citations formats

Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Related Articles

Article Metrics

Article Access Statistics



[Return to top]
Molecules EISSN 1420-3049 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top