2. Academic Validation
  3. Synthesis and in vitro anti-HIV evaluation of a new series of 6-arylmethyl-substituted S-DABOs as potential non-nucleoside HIV-1 reverse transcriptase inhibitors

Synthesis and in vitro anti-HIV evaluation of a new series of 6-arylmethyl-substituted S-DABOs as potential non-nucleoside HIV-1 reverse transcriptase inhibitors

  • Eur J Med Chem. 2009 Mar;44(3):1016-23. doi: 10.1016/j.ejmech.2008.06.028.
Yue-Ping Wang 1,  Fen-Er Chen,  Erik De Clercq,  Jan Balzarini,  Christophe Pannecouque
Affiliations

Affiliation

  • 1 Department of Chemistry, Fudan University, Shanghai 200433, PR China.
PMID: 18692274 DOI: 10.1016/j.ejmech.2008.06.028
Abstract

A series of new 5-alkyl-2-benzylsulfanylpyrimidin-4(3H)-ones (5a-y) bearing different substituted arylmethyl moieties at the C-6 position of the pyrimidine core have been synthesized and evaluated for their in vitro activities against HIV-1 and HIV-2 in MT-4 cell cultures. The majority of the title compounds showed moderate to good activities against HIV-1 with an IC(50) range from 6.67 microM to 0.12 microM. Among them, 6-(3,5-dimethylbenzyl) analogue 5q exhibited the most potent anti-HIV-1 activity (IC(50)=0.12 microM, SI>2642), which was about 40-fold more active than the reference compounds 1-[(2-hydroxyethoxy)methyl]-6-(phenylsulfanyl)thymine (HEPT) and 2',3'-dideoxyinosine (DDI). The structure-activity relationships (SARs) of these new congeners were further discussed.

Figures