Design, synthesis, and biological evaluation of novel tricyclic HIV-1 integrase inhibitors by modification of its pyridine ring

This communication details both the syntheses and biological evaluation of a novel class of HIV-1 integrase inhibitors. When the quinoline moiety is replaced with the quinoxoline moiety, the antiviral activity is significantly compromised. Similarly, introduction of imidazole to replace the pyridine ring is deleterious to the potency of the compound against the enzyme. Substitution at the 3-position of the pyridine has been investigated. The presence of the pyridine ring in the tricyclic core is preferred for antiviral activity against HIV integrase.

Graphical abstractA series of novel analogs of 1 were synthesized and biologically evaluated against HIV-1 integrase. The analogs made were modifications made to the pyridine ring with a variety of heterocycles and substitutions.Figure optionsDownload full-size imageDownload as PowerPoint slide