The medicinal chemistry and structure− activity relationships for a novel series of 7-benzyl-4- hydroxy-1, 5-naphthyridin-2 (1 H)-one HIV-integrase inhibitors are disclosed. Substituent effects were evaluated at the N-1, C-3, and 7-benzyl positions of the naphthyridinone ring system. Low nanomolar IC50 values were achieved in an HIV-integrase strand transfer assay with both carboxylic ester and carboxamide groups at C-3. More importantly, ...