1-(2-Carboxyindol-5-yloxy)propan-2-ones as inhibitors of human cytosolic phospholipase A2α: Synthesis, biological activity, metabolic stability, and solubility

Fritsche A, Elfringhoff AS, Fabian J, Lehr M

Zusammenfassung

Indole-5-carboxylic acids with 3-aryloxy-2-oxopropyl residues in position 1 were previously reported to be potent inhibitors of cytosolic phospholipase A2α (cPLA2α) isolated from human platelets. In continuation of our attempts to develop novel cPLA2α inhibitors, a series of structurally related indole-2-carboxylic acids containing 3-aryloxy-2-oxopropoxy residues in position 5 were synthesized and tested for their cPLA2α-inhibitory potency. Furthermore, the thermodynamic solubility of these compounds and their metabolic stability against rat liver microsomes were evaluated.