5-Lipoxygenase inhibitors: a review of recent patents (2010 – 2012)

Abstract

Introduction: 5-Lipoxygenase (5-LO) is a crucial enzyme of the arachidonic acid (AA) cascade and catalyzes the formation of bioactive leukotrienes (LTs) with the help of FLAP, the 5-LO-activating protein. LTs are inflammatory mediators playing a pathophysiological role in different diseases like asthma, allergic rhinitis as well as cardiovascular diseases and certain types of cancer. With the rising number of indications for anti-LT therapy, 5-LO inhibitor drug development becomes increasingly important.

Areas covered: Here, both recent findings regarding the pathophysiological role of 5-LO and the patents claimed for 5-LO inhibitors are discussed. Focusing on direct inhibitors, several patents disclosing FLAP antagonists are also subject of this review. Novel compounds include 1,5-diarylpyrazoles, indolizines and indoles and several natural product extracts.

Expert opinion: Evaluation of the patent activities revealed only quite moderate action. Nevertheless, several auspicious drug-like molecules were disclosed. It seems that in the near future, FLAP inhibitors can be expected to enter the market for the treatment of asthma. With the resolved structure of 5-LO, structure-based drug design is now applicable. Together with the identification of downstream enzyme inhibitors and dual-targeting drugs within the AA cascade, several tools are at hand to cope with 5-LOs increasing pathophysiological roles.

Keywords::

• 1,5-diarylpyrazoles
• 5-lipoxygenase inhibition
• asthma
• cancer
• cardiovascular diseases
• FLAP
• indoles
• indolizines
• inflammation
• leukemia

Declaration of interest

The authors gratefully acknowledge financial support by Fonds der Chemischen Industrie and the Else Kröner-Fresenius Foundation (TRIP). The authors declare no conflict of interest concerning the subjects of this paper.

Notes

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