2. Academic Validation
  3. Design, synthesis and anti-HIV evaluation of novel diarylpyridine derivatives as potent HIV-1 NNRTIs

Design, synthesis and anti-HIV evaluation of novel diarylpyridine derivatives as potent HIV-1 NNRTIs

  • Eur J Med Chem. 2017 Nov 10:140:383-391. doi: 10.1016/j.ejmech.2017.07.012.
Zhaoqiang Liu 1,  Ye Tian 1,  Jinghan Liu 2,  Boshi Huang 1,  Dongwei Kang 1,  Erik De Clercq 3,  Dirk Daelemans 3,  Christophe Pannecouque 3,  Peng Zhan 4,  Xinyong Liu 5
Affiliations

Affiliations

  • 1 Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012, Jinan, Shandong, PR China.
  • 2 School of Life Science and Technology, China Pharmaceutical University, 639 Longmian Avenue, 210009, Nanjing, PR China.
  • 3 Rega Institute for Medical Research, KU Leuven, Minderbroedersstraat 10, B-3000 Leuven, Belgium.
  • 4 Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012, Jinan, Shandong, PR China. Electronic address: zhanpeng1982@sdu.edu.cn.
  • 5 Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmaceutical Sciences, Shandong University, 44, West Culture Road, 250012, Jinan, Shandong, PR China. Electronic address: xinyongl@sdu.edu.cn.
PMID: 28987601 DOI: 10.1016/j.ejmech.2017.07.012
Abstract

As a continuation of our efforts to discover and develop "me-better" drugs of DAPYs, novel diarylpyridine derivatives were designed, synthesized and evaluated for their anti-HIV activities in MT-4 cells. The majority of these compounds showed high activity against wild-type HIV-1 strain (IIIB) with EC50 values in the range of 0.04-4.41 μM. Among them, compound 5b2 (EC50 = 0.04 μM, SI = 3963) was the most potent. This compound showed anti-HIV-1IIIB activity superior than of Nevirapine but still inferior than of Etravirine. Selected compounds were also evaluated for the activity against Reverse Transcriptase (RT), and most of the compounds exhibited submicromolar IC50 values indicating they are specific RT inhibitors. Preliminary structure-activity relationships and modeling studies of these new analogues provide valuable avenues for future molecular optimization.

Keywords

Bioisosteric principle; Drug design; HIV-1; NNRTIs; Pyridine.

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