Structure-activity Relationships of Substituted 1-pyridyl-2-phenyl-1,2-ethanediones: Potent, Selective Carboxylesterase Inhibitors

Overview

Journal J Med Chem

Publisher American Chemical Society

Specialty Chemistry

Date 2010 Nov 26

PMID 21105730

Citations 7

Authors

Brandon M Young

Janice L Hyatt

David C Bouck

Taosheng Chen

Parimala Hanumesh

Jeanine Price

Vincent A Boyd

Philip M Potter

Thomas R Webb

Affiliations

Soon will be listed here.

Abstract

Inhibition of intestinal carboxylesterases may allow modification of the pharmacokinetics/pharmacodynamic profile of existing drugs by altering half-life or toxicity. Since previously identified diarylethane-1,2-dione inhibitors are decidedly hydrophobic, a modified dione scaffold was designed and elaborated into a >300 member library, which was subsequently screened to establish the SAR for esterase inhibition. This allowed the identification of single digit nanomolar hiCE inhibitors that showed improvement in selectivity and measured solubility.

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