2. Academic Validation
  3. Synthesis and evaluation of sulfonamide derivatives as potent Human Uric Acid Transporter 1 (hURAT1) inhibitors

Synthesis and evaluation of sulfonamide derivatives as potent Human Uric Acid Transporter 1 (hURAT1) inhibitors

  • Bioorg Med Chem Lett. 2017 May 1;27(9):1919-1922. doi: 10.1016/j.bmcl.2017.03.041.
Xintuo Yang 1,  Xuehai Pang 1,  Lei Fan 2,  Xinghai Li 2,  Yuanwei Chen 3
Affiliations

Affiliations

  • 1 Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Sichuan 610041, China; University of Chinese Academy of Sciences, Beijing 100049, China.
  • 2 Hinova Pharmaceuticals Inc., Suite 301, Building B, #5 South KeYuan Road, Chengdu, Sichuan 610041, China.
  • 3 Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Sichuan 610041, China; University of Chinese Academy of Sciences, Beijing 100049, China; Hinova Pharmaceuticals Inc., Suite 301, Building B, #5 South KeYuan Road, Chengdu, Sichuan 610041, China. Electronic address: ywchen@scu.edu.cn.
PMID: 28351592 DOI: 10.1016/j.bmcl.2017.03.041
Abstract

This letter presents synthesis and structure-activity relationship study of sulfonamide derivatives as inhibitors of Human Uric Acid Transporter 1 (hURAT1). Among all tested sulfonamide derivatives, compounds 9b, 16i and 19b exhibited excellent inhibition activity with IC50 value of 10, 2, and 83nM, respectively. In addition, compounds 9b and 19b demonstrated moderate PK profile in rats.

Keywords

Bioisostere; Gout disease; Pharmacokinetic studies; Structure-activity relationship; Sulfonamide; hURAT1 inhibitor.

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