Synthesis and anti-HIV-1 activity of 4-substituted-7-(2′-deoxy-2′-fluoro-4′-azido-β-d-ribofuranosyl)pyrrolo[2,3-d]pyrimidine analogues

Abstract Three novel 4-subsituted-7-(2′-deoxy-2′-fluoro-4′-azido-β- d -ribofuranosyl)pyrrolo[2,3- d ]pyrimidine analogues were designed, synthesized, and tested for their anti-HIV-1 activity. Initial biological studies indicated that among these pyrrolo[2,3- d ]pyrimidine ribonucleoside analogues, 4-amino-7-(2′-deoxy-2′-fluoro-4′-azido-β- d -ribofuranosyl)pyrrolo[2,3- d ]pyrimidine 10 exhibited the most potent anti-HIV-1 activity (EC 50  = 0.5±0.3 μM), while 4-hydroxy-7-(2′-deoxy-2′-fluoro-4′-azido-β- d -ribofuranosyl)pyrrolo[2,3- d ] pyrimidine 9 and 4-amino-5-fluoro-7-(2′-deoxy-2′-fluoro-4′-azido-β- d -ribofuranosyl)pyrrolo[2,3- d ] pyrimidine 11 showed moderate activity (EC 50  = 13 ± 8 and 5.4 ± 0.3 μM, respectively). The cytotoxicity of these compounds has also been assessed. No significant cytotoxicities were found for any of these compounds with concentrations up to 25 μM.