2. Academic Validation
  3. Synthesis and biological evaluation of CHX-DAPYs as HIV-1 non-nucleoside reverse transcriptase inhibitors

Synthesis and biological evaluation of CHX-DAPYs as HIV-1 non-nucleoside reverse transcriptase inhibitors

  • Bioorg Med Chem. 2014 Jun 15;22(12):3220-6. doi: 10.1016/j.bmc.2014.03.020.
Zi-Hong Yan 1,  Hai-Qiu Wu 1,  Wen-Xue Chen 1,  Yan Wu 2,  Hu-Ri Piao 2,  Qiu-Qin He 3,  Fen-Er Chen 4,  Erik De Clercq 5,  Christophe Pannecouque 5
Affiliations

Affiliations

  • 1 Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China.
  • 2 College of Pharmacy, Yanbian University, Yanji 133000, People's Republic of China.
  • 3 Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China. Electronic address: qqhe@fudan.edu.cn.
  • 4 Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China; Institute of Biomedical Science, Fudan University, Shanghai 200433, People's Republic of China. Electronic address: rfchen@fudan.edu.cn.
  • 5 Rega Institute for Medical Research, Katholieke Universiteit Leuven, 10 Minderbroedersstraat, B-3000 Leuven, Belgium.
PMID: 24794751 DOI: 10.1016/j.bmc.2014.03.020
Abstract

A series of new diarylpyrimidines (DAPYs) characterized by a halogen atom on the methylene linker between wing I and the central pyrimidine ring was synthesized and evaluated for their anti-HIV activity in MT-4 cell cultures. The two most promising compounds 7f and 7g showed excellent activity against wild-type HIV-1 with low nanomolar EC50 values of 0.005 and 0.009 μM, respectively, which were comparable to or more potent than all the reference drugs zidovudine (AZT), lamivudine (3TC), nevirapine (NEV), efavirenz (EFV), delaviridine (DLV) and etravirine (ETV). In particular, 7g also displayed strong activity against the double mutant strain 103N + 181C with an EC50 value of 8.2 μM. The preliminary structure-activity relationship (SAR) and molecular docking analysis of this new series of CHX-DAPYs were also investigated.

Keywords

Antiviral activity; Diarylpyrimidine; HIV-1; NNRTIs; SAR.

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