Synthesis and Biological Evaluation of Novel 2-Arylalkylthio-5-iodine-6-substituted-benzyl-pyrimidine-4(3H)-ones as Potent HIV-1 Non-Nucleoside Reverse Transcriptase Inhibitors

Molecules

Liang Zhang¹  Xiaowan Tang¹  Yuanyuan Cao¹  Shaotong Wu¹  Yu Zhang¹  Jianxiong Zhao¹  Ying Guo¹  Chao Tian¹  Zhili Zhang¹  Junyi Liu¹ 

[1] Department of Chemical Biology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China

关键词: HIV;    NNRTIs;    S-DABOs;    IC₅₀;    docking;   

DOI  :  10.3390/molecules19067104

来源: mdpi

【 摘 要 】

A novel series of 2-arylalkylthio-5-iodine-6-substitutedbenzyl-pyrimidine-4(3H)-ones (S-DABOs) 8a–x had been synthesized via an efficient method. Their biological activity against HIV virus and RT assay were evaluated. Some compounds, especially 8h, 8l and 8n, displayed promising activity against HIV-1 RT with IC₅₀ values in a range of 0.41 μM to 0.71 μM, which were much better than that of nevirapine. Molecular modeling studies revealed that the binding mode would be affected via forming an additional hydrogen bond by incorporating an oxygen atom on the C-2 side chain. The biological activity was in accordance with the docking results.

【 授权许可】

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