Synthesis of New Alicyclic Oxalamide Derivatives and Their Differential Immunomodulatory Activities on the Mammalian Cells

Abstract

A series of novel alicyclic oxalamide derivatives were synthesized by the reaction of the N-alicyclic secondary amine analogs with the intermediates obtained from the reaction of 2-aminophenol derivatives and diethyl oxalate. Due to their similarities to the thalidomide, these compounds were synthesized as alternative anti-inflammatory drug candidates. In order to test their efficacies, an in vitro inflammation model was utilized. In this model, macrophages be activated by a danger mimic lipopolysaccharide to produce pro-inflammatory cytokines. Macrophages are the major cell types that produce cytokines against danger stimuli to regulate the local as well as systemic immune reactions. The alicyclic oxalamide derivatives' immunomodulatory potentials were tested in vitro on the macrophages. Based on our results, these molecules had differential effects on the production of the TNF alpha and IL6 pro-inflammatory cytokines by the lipopolysaccharide-stimulated macrophages. A set of the derivatives had adjuvant and immunostimulatory activities, while another group had anti-inflammatory activities. Their differential effects on the production of the TNF alpha and IL6 open new venues for their medicinal applications. One can target a specific cytokine that has been associated with a certain disease while sparing the activity and production of the other cytokine by using a certain selection of the derivatives in our hands.