PLA-Inhibitors (stoPLA): New class of NSAIDs for oral and transdermal pain treatment
Phospholipase A2 (PLA2) designates a large and diverse
group of enzymes that cleave phospholipids at the sn-2- position. This metabolic step is instrumental in a variety of pathogenic processes causing pain, fever and inflammation. Presently glucocortidoids are used for inhibition of PLA2. Unfortunately, glucocortidoids have serious side effects which limit their use as medication for pain treatment. stoPLA is a new class of heteroaryl-substituted acetone derivatives for the effective inhibition of PLA2, especially of cytosolic PLA2. These compounds effectively interact with the synthesis of prostaglandins and leukotrienes and reduce inflammatory processes. The new heteroarylsubstituted acetone derivatives have also an excellent solubility profile and are stable against metabolic inactivation through ketogroup reduction.
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