Synthesis and biological evaluation of novel C5 halogen-functionalized S-DABO as potent HIV-1 non-nucleoside reverse transcriptase inhibitors

A series of novel S-DABO analogues (4a1–5a12) have been synthesized by an efficient method and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). The biological testing results clearly indicated that the substitution of halogen at the C5 position of pyrimidine ring could increase the anti-HIV-1 RT activity. The most active compounds showed activity in the low micromole range with IC50 values (IC50 0.18–3.03 μM) comparable to nevirapine (IC50 4.12 μM). The docking showed that a new halogen bond was formed between halogen and carbonyl of TYR188 in the HIV-I RT.

A halogen bond between the C5-I and the carbonyl of TYR188 could increase the activity to HIV-1 RT.Figure optionsDownload as PowerPoint slide