Synthesis and biological evaluation of novel dihydro-aryl/alkylsulfanyl-cyclohexylmethyl-oxopyrimidines (S-DACOs) as high active anti-HIV agents

Bioorg Med Chem Lett. 2011 Jan 15;21(2):694-7. doi: 10.1016/j.bmcl.2010.12.003. Epub 2010 Dec 7.

Abstract

A novel dihydro-aryl/alkylsulfanyl-cyclohexylmethyl-oxopyrimidines (S-DACOs) combinatory library was synthesized and evaluated with C8166 cells infected by the HIV-1(IIIB) in vitro, using Nevirapine (NVP) and Zidovudine (AZT) as positive control. The anti-HIV screening results revealed that C-6-cyclohexylmethyl substituted pyrimidinones possessed higher selective index than its 6-arylmethyl counterparts. Compounds 1g, 1c, 1e and 1b showed potent anti-HIV activities with EC(50) values of 0.012, 0.025, 0.088 and 0.162nM, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / pharmacology*
  • Cell Line
  • HIV Infections / drug therapy*
  • HIV-1 / drug effects*
  • Humans
  • Leukocytes, Mononuclear / virology
  • Nevirapine / pharmacology
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / pharmacology*
  • Structure-Activity Relationship
  • Zidovudine / pharmacology

Substances

  • Anti-HIV Agents
  • Pyrimidines
  • Zidovudine
  • Nevirapine