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.
References
Dec 1, 1992·Toxicology Letters·S GreenI Issemann
Aug 1, 1992·Trends in Pharmacological Sciences·R M McMillan, E R Walker
Jun 1, 1988·British Journal of Pharmacology·J E TatesonL G Garland
Dec 1, 1984·Journal of Medicinal Chemistry·G d'AtriC R Sirtori
Jan 1, 1994·Annual Review of Biochemistry·A W Ford-HutchinsonR N Young
Aug 4, 1998·Molecular Pharmacology·O WerzD Steinhilber
Jan 25, 2002·Blood·Oliver WerzDieter Steinhilber
Sep 21, 2004·Shock·Salvatore CuzzocreaAchille P Caputi
May 24, 2005·Biochemical Pharmacology·Oliver Werz, Dieter Steinhilber
Dec 14, 2005·The Biochemical Journal·Raquel GrauMiguel A Iñiguez
Jul 14, 2006·Pharmacology & Therapeutics·Oliver Werz, Dieter Steinhilber
Jul 26, 2006·Free Radical Biology & Medicine·Massimo CollinoRoberto Fantozzi
Aug 23, 2006·Proceedings of the National Academy of Sciences of the United States of America·Marija RakonjacOlof Rådmark
Jun 20, 2007·Trends in Biochemical Sciences·Olof RådmarkBengt Samuelsson
Jul 5, 2007·Archiv der Pharmazie·Laura PopescuManfred Schubert-Zsilavecz
Oct 17, 2007·Planta medica·Oliver Werz
Nov 6, 2007·The New England Journal of Medicine·Marc Peters-Golden, William R Henderson
Jan 12, 2008·Trends in Pharmacological Sciences·Jilly F EvansJohn H Hutchinson
Feb 16, 2008·Archiv der Pharmazie·Oliver RauManfred Schubert-Zsilavecz
Citations
May 20, 2011·Journal of Medicinal Chemistry·Martina HiekeOliver Werz
Nov 1, 2013·Journal of Medicinal Chemistry·Thomas HankeOliver Werz
Feb 6, 2014·PloS One·Sangchul LeeSung-Jun Han
Oct 26, 2011·Future Medicinal Chemistry·Hui-Hua Chang, Emmanuelle J Meuillet
Feb 24, 2016·Acta Pharmaceutica Sinica. B·Yu ZhouHong Liu
Aug 19, 2009·European Journal of Pharmacology·Daniel PoeckelOliver Werz
Mar 18, 2011·British Journal of Pharmacology·M RevermannD Steinhilber
Apr 22, 2011·British Journal of Pharmacology·C GreinerO Werz
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
Dec 7, 2011·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Matthias Gabler, Manfred Schubert-Zsilavecz
Nov 27, 2010·Archiv der Pharmazie·Michaela DittrichManfred Schubert-Zsilavecz
Feb 26, 2010·Expert Opinion on Therapeutic Patents·Carlo Pergola, Oliver Werz
Nov 26, 2009·The Journal of Pharmacology and Experimental Therapeutics·Andreas KoeberleOliver Werz
Feb 18, 2016·Oncotarget·Martin MichaelisJindrich Cinatl
Dec 5, 2008·Journal of Medicinal Chemistry·Andreas KoeberleOliver Werz
Apr 5, 2014·Journal of Medicinal Chemistry·Carlo PergolaOliver Werz