2. Academic Validation
  3. Design and synthesis of a novel series of non-nucleoside HIV-1 inhibitors bearing pyrimidine and N-substituted aromatic piperazine

Design and synthesis of a novel series of non-nucleoside HIV-1 inhibitors bearing pyrimidine and N-substituted aromatic piperazine

  • Bioorg Med Chem Lett. 2018 Dec 1;28(22):3491-3495. doi: 10.1016/j.bmcl.2018.10.010.
KaiJun Jin 1,  YaLi Sang 1,  Erik De Clercq 2,  Christophe Pannecouque 2,  Ge Meng 3
Affiliations

Affiliations

  • 1 Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai 200433, People's Republic of China.
  • 2 Rega Institute for Medical Research, KU Leuven, Herestraat 49, B-3000 Leuven, Belgium.
  • 3 Engineering Center of Catalysis and Synthesis for Chiral Molecules, Department of Chemistry, Fudan University, Shanghai 200433, People's Republic of China; Shanghai Engineering Center of Industrial Asymmetric Catalysis for Chiral Drugs, Shanghai 200433, People's Republic of China. Electronic address: mgfudan@fudan.edu.cn.
PMID: 30318436 DOI: 10.1016/j.bmcl.2018.10.010
Abstract

A novel series of substituted piperazine-1-yl-pyrimidine derivatives were designed and synthesized as a new type of HIV-1 non-nucleoside inhibitors. Various N-substituted aromatic groups were incorporated into the piperazine ring through a simple and practical route to investigate the biological activity of these target compounds against wild-type and resistant strains of HIV-1. All of the target compounds were also evaluated as HIV-1 Reverse Transcriptase inhibitors in MT-4 cell cultures. The biological results showed that six of these compounds displayed inhibitory activities against the wild-type strain, among of which 7q and 7t were found to be the two most active analogues possessing EC50 values of 31.50 μM and 3.36 μM, respectively. Molecular modeling studies of 7q provide valuable information for developing new anti-HIV-1 inhibitors.

Keywords

Diarylpyrimidine; HIV-1; Molecular modeling; Piperazine; Reverse transcriptase.

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