5-Acyl 3-Substituted Benzofuran-2(3H)-ones as Potential Antiinflammatory Agents.

A series of 5-acyl-3-substituted-benzofuran-2(3H)-ones and their respective ring-opened o-hydroxy acids were synthesized. The antiinflammatory activity was evaluated in terms of their ability to improve adjuvant induced arthritis in rats. Their effect on the production of both cyclooxygenase (CO) and lipoxygenase (LO) metabolites of arachidonic acid in guinea pig peritoneal polymorphonuclear neutrophils (PMNs) was also examined. No correlation between the antiinflammatory activity and increasing stability of the lactones could be found. The degree of activity in general shown by the benzofuranones was similar to that of their corresponding o-hydroxy acids. This, coupled with the evidence from studies on opening of the lactone ring, suggests an in vivo transformation of the former into the latter. Benzofuranones displayed a dual inhibition of CO and LO products, while a moderate reduction in CO metabolites was shown by their acids.