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

被引：10

作者：

Zhang, Liang ^{[1
]}

Tang, Xiaowan ^{[1
]}

Cao, Yuanyuan ^{[1
]}

Wu, Shaotong ^{[1
]}

Zhang, Yu ^{[1
]}

Zhao, Jianxiong ^{[1
]}

Guo, Ying ^{[1
]}

Tian, Chao ^{[1
]}

Zhang, Zhili ^{[1
]}

Liu, Junyi ^{[1
,2
]}

Wang, Xiaowei ^{[1
]}

机构：

[1] Peking Univ, Dept Biol Chem, Sch Pharmaceut Sci, Beijing 100191, Peoples R China

[2] Peking Univ, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China

来源：

MOLECULES | 2014年 / 19卷 / 06期

关键词：

HIV; NNRTIs; S-DABOs; IC50; docking; IMMUNODEFICIENCY-VIRUS TYPE-1; S-DABO DERIVATIVES; ANTI-HIV-1; ACTIVITY; URACIL DERIVATIVES; IN-VITRO; DESIGN; RESISTANCE; DRUGS;

D O I：

10.3390/molecules19067104

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

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 mu M to 0.71 mu M, 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.

引用

页码：7104 / 7121

页数：18

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