title: 5-Lipoxygenase inhibitors: a review of recent patents (2010-2012).
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Goethe University Frankfurt, Institute of Pharmaceutical Chemistry, Max-von-Laue-Str. 9, 60438, Frankfurt, Germany.
authors.forename: Bettina
authors.initials: B
authors.lastname: Hofmann
authors.forename: Dieter
authors.initials: D
authors.lastname: Steinhilber
mesh_terms: D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000187:drug effects* / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology; D015195:Drug Design; D006801:Humans; D007249:Inflammation / Q000188:drug therapy / Q000503:physiopathology; D016859:Lipoxygenase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D058990:Molecular Targeted Therapy; D010330:Patents as Topic; D013329:Structure-Activity Relationship
chemical_list: D016859:Lipoxygenase Inhibitors; D016718:Arachidonic Acid; D001094:Arachidonate 5-Lipoxygenase