Novel and potent inhibitors of 5-lipoxygenase product synthesis based on the structure of pirinixic acid

Journal of Medicinal Chemistry
Oliver WerzD Steinhilber

Abstract

A novel class of potent 5-lipoxygenase (5-LO) product synthesis inhibitors based on the structure of pirinixic acid (4-chloro-6-(2,3-xylidino)-2-pyrimidinylthioacetic acid, compound 1) is presented. Systematic profiling of 1, i.e., esterification of the carboxylic acid, alpha-substitution, and replacement of the o-dimethylaniline by 6-aminoquinoline, leads to potent suppressors of 5-LO product formation in activated polymorphonuclear leukocytes, exemplified by ethyl 2-[4-chloro-6-(quinoline-6-ylamino)-pyrimidin-2-ylsulfanyl]octane-1-carboxylate (6d, IC50 = 0.6 microM). These derivatives may possess potential for intervention with inflammatory and allergic diseases.

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Citations

Oct 26, 2011·Future Medicinal Chemistry·Hui-Hua Chang, Emmanuelle J Meuillet
May 26, 2010·Journal of Internal Medicine·O Rådmark, B Samuelsson
Aug 28, 2015·Future Medicinal Chemistry·Daniel MerkManfred Schubert-Zsilavecz
Jul 19, 2016·Journal of Enzyme Inhibition and Medicinal Chemistry·Shima DianatAlireza Foroumadi
Nov 27, 2010·Archiv der Pharmazie·Michaela DittrichManfred Schubert-Zsilavecz
Feb 26, 2010·Expert Opinion on Therapeutic Patents·Carlo Pergola, Oliver Werz

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