2. Academic Validation
  3. Novel and potent inhibitors of 5-lipoxygenase product synthesis based on the structure of pirinixic acid

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

  • J Med Chem. 2008 Sep 11;51(17):5449-53. doi: 10.1021/jm800588x.
Oliver Werz 1,  Christine Greiner,  Andreas Koeberle,  Christina Hoernig,  Sven George,  Laura Popescu,  Ivonne Syha,  Manfred Schubert-Zsilavecz,  Dieter Steinhilber
Affiliations

Affiliation

  • 1 Department of Pharmaceutical Analytics, Pharmaceutical Institute, Eberhard-Karls-University Tuebingen, Auf der Morgenstelle 8, D-72076 Tuebingen, Germany. oliver.werz@uni-tuebingen.de
PMID: 18710209 DOI: 10.1021/jm800588x
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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