Structure-activity relationship studies on (4-acylpyrrol-2-yl)alkanoic acids as inhibitors of the cytosolic phospholipase A 2: Variation of the alkanoic acid substituent, the acyl chain and the position of the pyrrole nitrogen

Abstract

Summary (4-Acylpyrrol-2-yl)alkanoic acid derivatives were prepared and evaluated for their ability to inhibit the cytosolic phospholipase A 2 of intact bovine platelets. To define the structural requirements for enzyme inhibition, the alkanoic acid group, the acyl residue and the position of the pyrrole nitrogen relative to the pyrrole substituents were varied systematically. Inhibition of cPLA 2 was best by compounds containing a free acetic acid or propionic acid group and an acyl chain of 12 or more carbons. The position of the pyrrole nitrogen did not influence the activity significantly. One of the most potent of the cPLA 2 inhibitors synthesized was (1,3,5-trimethyl-4-octadecanoylpyrrol-2-yl)acetic acid (IC 50 : 10 μM).