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

• Published in: Bioorganic & medicinal chemistry letters 2011-11, Vol.21 (22), p.6770-6772
• Main Authors: Guo, Xiaohe, Li, Yujiang, Tao, Le, Wang, Qiang, Wang, Shuyang, Hu, Weidong, Pan, Zhenliang, Yang, Qinghua, Cui, Yanmei, Ge, Zhaopeng, Dong, Lihong, Yu, Xuejun, An, Haoyun, Song, Chuanjun, Chang, Junbiao
• Format: Article
• Language: English
• Subjects: Anti-HIV Agents - chemical synthesis; Anti-HIV Agents - chemistry; Anti-HIV Agents - pharmacology; Anti-HIV-1 activity; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral agents; antiviral properties; Biological and medical sciences; chemical derivatives; cytotoxicity; HIV Infections - drug therapy; HIV-1 - drug effects; Human immunodeficiency virus 1; Humans; Medical sciences; Pharmacology. Drug treatments; pyrimidines; Pyrimidines - chemical synthesis; Pyrimidines - chemistry; Pyrimidines - pharmacology; pyrroles; Pyrroles - chemical synthesis; Pyrroles - chemistry; Pyrroles - pharmacology; Pyrrolo[2,3- d]pyrimidine; Ribonucleoside; Ribonucleosides - chemical synthesis; Ribonucleosides - chemistry; Ribonucleosides - pharmacology; Synthesis
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2011.09.040

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.