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Novel selective h-mPGES-1 inhibitors for inflammation and cancer
[Category : - HEALTH- Organic Chemistry]
[Viewed 989 times]
BUSINESS POTENTIAL
Prostaglandin E2 (PGE2) is a key lipid mediator of the progression of inflammation and cancer, and it is metabolically produced from arachidonic acid by the action of mPGES-1 enzyme. Inhibition of cyclooxygenase (COX) enzymes by non-steroidal anti-inflammatory drugs (NSAIDs) reduces prostanoid levels including PGE2, although showing several undesired side effects. Therefore, the identification of selective inhibitors of PGE2 production would constitute a safer therapeutic strategy.
PATENTS SUMMARY
The technology relates to four patent families disclosing novel 3-aminocarbazole (among which the lead compound AF3485), 2-arylindole, and (aza)indole compounds capable to inhibit PGE2 production by the selective inhibition of mPGES-1 enzyme in the micromolar range. Described compounds are being developed as new agents for the treatment or prevention of inflammatory processes, tumors, Alzheimer’s disease and atherosclerosis, with potential reduced gastrointestinal, renal and vascular toxicity compared to NSAIDs. Furthermore, the molecules do not significantly inhibit cytosolic PGES-1 enzyme. The technology also includes intermediate compounds, derivatives among which physiologically acceptable addition salts, and preparation process.
COMPETITIVE ADVANTAGE
The ability to selectively inhibit mPGES-1 makes these molecules potential therapeutics for inflammatory diseases, and at the same time potentially safer drugs with fewer side effects than NSAID drugs currently in use because of no reduction of other lipid mediators in the arachidonic acid cascade.
Patent publications:
WO 2007014687
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