Abstract
The serine hydrolases cytosolic phospholipase A(2)α (cPLA(2)α) and fatty acid amide hydrolase (FAAH) are interesting targets for the development of new anti-inflammatory and analgesic drugs. Structural modifications of a potent dual inhibitor with a propan-2-one substituted tetrazolylpropionic acid moiety led to compounds with also nanomolar activity against both enzymes but better physicochemical properties. The structure-activity relationships showed that the variations had partially divergent effects on the inhibitory activity of the compounds towards cPLA(2)α and FAAH reflecting differences in the binding mode to the enzymes. Furthermore, the metabolic stability of the target structures was investigated in vitro.