title: Human uric acid transporter 1 (hURAT1): an inhibitor structure-activity relationship (SAR) study.
abstract: The current study describes the chemical synthesis of a series of (2-ethylbenzofuran-3-yl)(substituted-phenyl)methanone compounds and their subsequent in vitro testing via oocytes expressing hURAT1. The experimental data support the notion that a potent hURAT1 inhibitor requires an anion (i.e., a formal negative charge) to interact with the positively charged hURAT1 binding pocket. An anion appears to be a primary requirement in order to be a hURAT1 substrate (i.e., urate) or inhibitor. We discuss the inhibitor structure-activity relationship and how electronically donating or withdrawing groups attached to the B-ring can decrease or increase inhibitory potency, respectively.
authors: School of Pharmacy, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA. Michael.Wempe@ucdenver.edu
authors: M F
authors: MF
authors: Wempe
authors: B
authors: B
authors: Quade
authors: P
authors: P
authors: Jutabha
authors: T
authors: T
authors: Iwen
authors: M
authors: M
authors: Frick
authors: P J
authors: PJ
authors: Rice
authors: S
authors: S
authors: Wakui
authors: H
authors: H
authors: Endou
mesh_terms: D000838:Anions; D047188:Chalcones / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D027361:Organic Anion Transporters / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D027701:Organic Cation Transport Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry* / Q000378:metabolism; D013329:Structure-Activity Relationship; D014527:Uric Acid / Q000737:chemistry / Q000378:metabolism
chemical_list: D000838:Anions; D047188:Chalcones; D027361:Organic Anion Transporters; D027701:Organic Cation Transport Proteins; C491241:SLC22A12 protein, human; D014527:Uric Acid