Inhibitors of 5-lipoxygenase activating protein: WO 2008/030369.
BACKGROUND
5-Lipoxygenase activating protein (FLAP) has been implicated in a number of different pathophysiological conditions owing to its involvement in leukotriene synthesis. Development of FLAP inhibitors has attracted considerable attention in recent years owing to genetic data supporting their potential as a valid pharmacological approach in prevention or treatment of atherosclerotic disease.


OBJECTIVE
Since 2005, among other companies, Merck applied for several FLAP inhibitor patents. Patent WO 2008/030369 is the most recent and discloses novel molecules that act as potent inhibitors of FLAP. These compounds are claimed to be useful in the treatment of atherosclerosis, asthma, symptoms of allergic rhinitis and chronic obstructive pulmonary disease either in monotherapy or in combination with established treatments for the above-mentioned disorders. Although data for the potency of representative molecules from the current patent are reported, it is difficult to compare these compounds with previously described compounds.


CONCLUSIONS
Two FLAP inhibitors are already in clinical development for the treatment of respiratory and atherosclerotic disease by other pharmaceutical companies. Based on the in vitro activities of representative tested compounds from this patent, it is probable that these agents could be of therapeutic value but further preclinical studies are needed to evaluate their therapeutic potential and safety before clinical development.
Tavridou
Anna
A
Lab of Pharmacology, Medical School, Democritus University of Thrace, Dragana Campus, Alexandroupolis, Greece. atavrid@med.duth.gr
Manolopoulos
Vangelis G
VG
D058927:5-Lipoxygenase-Activating Proteins; D000814:Aniline Compounds / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001249:Asthma / Q000188:drug therapy* / Q000378:metabolism; D050197:Atherosclerosis / Q000188:drug therapy* / Q000378:metabolism; D002317:Cardiovascular Agents / Q000737:chemistry / Q000494:pharmacology*; D002352:Carrier Proteins / Q000037:antagonists & inhibitors*; D006801:Humans; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D010330:Patents as Topic; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*; D019141:Respiratory System Agents / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
D058927:5-Lipoxygenase-Activating Proteins; C548592:ALOX5AP protein, human; D000814:Aniline Compounds; D002317:Cardiovascular Agents; D002352:Carrier Proteins; D008565:Membrane Proteins; D011725:Pyridines; D019141:Respiratory System Agents