Identification of Human Toll-like Receptor 2-Agonistic Activity in Dihydropyridine–Quinolone Carboxamides

Abstract

Using a multiplexed, reporter gene-based, high-throughput screen, we identified 9-fluoro-7-hydroxy-3-methyl-5-oxo-<i>N</i>-(pyridin-3-ylmethyl)-2,3-dihydro-1<i>H</i>,5<i>H</i>-pyrido[3,2,1-ij]quinoline-6-carboxamide as a TLR2 agonist. Preliminary structure-activity relationship studies on the carboxamide moiety led to the identification of analogues that induce chemokines and cytokines in a TLR2-dependent manner. These results represent new leads for the development of vaccine adjuvants.