title: Synthesis and evaluation of sulfonamide derivatives as potent Human Uric Acid Transporter 1 (hURAT1) inhibitors.
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 IC50value of 10, 2, and 83nM, respectively. In addition, compounds 9b and 19b demonstrated moderate PK profile in rats.
authors.affiliation: Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Sichuan 610041, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Xintuo
authors.initials: X
authors.lastname: Yang
authors.affiliation: Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu, Sichuan 610041, China; University of Chinese Academy of Sciences, Beijing 100049, China.
authors.forename: Xuehai
authors.initials: X
authors.lastname: Pang
authors.affiliation: Hinova Pharmaceuticals Inc., Suite 301, Building B, #5 South KeYuan Road, Chengdu, Sichuan 610041, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Fan
authors.affiliation: Hinova Pharmaceuticals Inc., Suite 301, Building B, #5 South KeYuan Road, Chengdu, Sichuan 610041, China.
authors.forename: Xinghai
authors.initials: X
authors.lastname: Li
authors.affiliation: 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.
authors.forename: Yuanwei
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D006073:Gout / Q000188:drug therapy / Q000201:enzymology; D006074:Gout Suppressants / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D008297:Male; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors* / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D006074:Gout Suppressants; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; D013449:Sulfonamides
keywords: Bioisostere; Gout disease; Pharmacokinetic studies; Structure-activity relationship; Sulfonamide; hURAT1 inhibitor