Structure-based linker optimization of 6-(2-cyclohexyl-1-alkyl)-2-(2-oxo-2-phenylethylsulfanyl)pyrimidin-4(3H)-ones as potent non-nucleoside HIV-1 reverse transcriptase inhibitors

被引：0

作者：

Daxiong Li ^{[1
]}

Chunsheng Zhang ^{[1
,2
]}

Wei Ding ^{[1
]}

Siming Huang ^{[1
]}

Le Yu ^{[1
]}

Nan Lu ^{[1
]}

Wenkai Pan ^{[1
]}

Yiming Li ^{[1
]}

Erik De Clercq ^{[3
]}

Christophe Pannecouque ^{[3
]}

Hongbing Zhang ^{[1
]}

Yueping Wang ^{[4
]}

Yanping He ^{[1
]}

Fener Chen ^{[5
]}

机构：

[1] Key Laboratory of Medicinal Chemistry for Natural Resource,Ministry of Education,Yunnan Research & Development Center for Natural Products,School of Chemical Science and Technology,Yunnan University

[2] Office of Academic Affairs,Yunnan University of Finance and Economics

[3] Rega Institute for Medical Research

[4] Department of Applied Chemistry,Faculty of Science,Kunming University of Science and Technology

[5] Engineering Center of Catalysis and Synthesis for Chiral Molecules,Department of Chemistry,Fudan University

来源：

Chinese Chemical Letters | 2021年 / 32卷 / 03期

关键词：

NNRTIs; S-DABOs; S-DACOs; Anti HIV-1 activity; SAR;

D O I：

暂无

中图分类号：

TQ460.1 [基础理论];

学科分类号：

1007 ;

摘要：

In continuation of our efforts toward the discovery of potent HIV-1 NNRTIs with diverse structures,a series of novel S-DACO analogues of 6-（2-cyclohexyl-1-allkyl）-2-（2-oxo-2-phenyl-ethylsulfanyl）pyrimidin-4（3 H）-ones were designed,synthesized and evaluated for their antiviral activities in MT-4 cells.Most of these new compounds showed moderate to good activities against wild type HIV-1 with IC50 values ranging from 7.55 μmol/L to 0.018 μmol/L.Among them,compound 5 c was identified as the most promising inhibitor against HIV-1 replication with an IC50=0.018 μmol/L,CC50=194 μmol/L,and SI=12791,which was much more potent than the reference drugs NVP and DLV and comparable to AZT and EFV.In addition,5 c also exhibited improved activity against double mutant HIV-1 strain RES056 compared to that of the reference drugs NVP/DLV and DB02.The preliminary structure-activity relationship（SAR） and molecular modeling studies were also discussed,which provides some useful indications for guiding the further rational design of new S-DACO analogues.

引用

页码：1020 / 1024

页数：5

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