Synthesis, activity and metabolic stability of propan-2-one substituted tetrazolylalkanoic acids as dual inhibitors of cytosolic phospholipase A₂α and fatty acid amide hydrolase

Abstract

The serine hydrolases cytosolic phospholipase A2α (cPLA2α) and fatty acid amide hydrolase (FAAH) are interesting targets for the development of new anti-inflammatory and analgesic drugs. Structural modifications of a potent...

1-Benzylindoles as inhibitors of cytosolic phospholipase A2α: synthesis, biological activity, aqueous solubility, and cell permeability

“…The aliphatic carboxylic acids were chosen in part because a recent study of cPLA 2 α inhibitory propan-2-ones showed that a compound containing a tetrazolylpropionic acid residue had particularly good water solubility. 19 Biochemical analysis revealed that all compounds in which the tetrazole ring was directly bound to the indole ( 68 , 70 , 72 , 74 ) were only very weak inhibitors of cPLA 2 α (Table 5). Their IC 50 values were around or above 10 μM.…”