Nucleosides, nucleotides and nucleic acids p. 1312 - 1323 (2011)
Update date:2022-08-03
Topics:
Wempe
Quade
Jutabha
Iwen
Frick
Rice
Wakui
Endou
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. Copyright Taylor and Francis Group, LLC.
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