Synthesis, activity, metabolic stability and cell permeability of new cytosolic phospholipase A2α inhibitors with 1-indolyl-3-phenoxypropan-2-one structure

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

“…11 However, these substances were also unsuitable for peroral use, as they are potent substrates of efflux transporters of intestinal cells and are also very quickly reduced in the body by carbonyl reductases to inactive alcohol derivatives. 11,12 To identify new lead structures for cPLA 2 α inhibitors, recently, we have performed a virtual screening 13 inspired by the work of Naylor et al and Gianella-Borradori et al 14,15 Energetically favourable conformers were calculated from a set of structurally related cPLA 2 α inhibitors of Wyeth (now Pfizer) with high potency, 7,10 such as WAY-196025 ( 2 ). Of the compounds that were the closest match, several were purchased and tested.…”