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PLA–Inhibitor (stoPLA) - New class of NSAIDs for oral and transdermal inflammation treatment

PLA2 enzymes cleave phospholipids at the sn-2-position.

They exist as secreted and cytosolic forms. The cytosolic PLA2 (cPLA2) appears to play a key role in the pathway leading to the formation of inflammatory lipid mediators such as prostaglandins, leukotrienes and platelet activating factor, thus this enzyme is instrumental in

pathogenic processes causing pain and inflammation. Presently topical application of glucocorticoids constitutes the most common way in the treatment of inflammatory dermatological disorders. Unfortunately, exposure of glucocorticoids has serious side effects, like skin atrophia, which limit their use as medication for inflammatory dermatitis. stoPLA is a new class of heteroaryl-substituted acetone derivatives for the effective inhibition of cytosolic PLA2 (cPLA2). These compounds effectively interact with the synthesis of prostaglandins and leukotrienes and reduce inflammatory processes. The new heteroaryl-substituted acetone derivatives have also an excellent solubility profile and are stable against metabolic inactivation through ketogroup reduction.

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