Synthesis and anti-HIV activity evaluation of 1-[(alkenyl or alkynyl or alkyloxy)methyl]-5-alkyl-6-(1-naphthoyl)-2,4-pyrimidinediones as novel non-nucleoside HIV-1 reverse transcriptase inhibitors

Eur J Med Chem. 2007 Feb;42(2):198-204. doi: 10.1016/j.ejmech.2006.09.018. Epub 2006 Nov 13.

Abstract

The synthesis and anti-HIV activity evaluation of a new series of 2,4-pyrimidinediones bearing a 6-(1-naphthoyl) group are described. In general, it was found that most of the title compounds showed good activities against human immunodeficiency virus type-1 (HIV-1). In particular, compound 26 displayed the most potent anti-HIV-1 activity (IC(50)=0.11+/-0.05 microM), inhibiting HIV-1 replication in MT-4 cells more effectively than HEPT (by 45-fold) and DDI (by 50-fold).

MeSH terms

  • Alkenes / chemical synthesis*
  • Alkenes / pharmacology
  • Alkynes / chemical synthesis*
  • Alkynes / pharmacology
  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / chemistry
  • Anti-HIV Agents / pharmacology
  • Cell Line, Tumor
  • HIV Reverse Transcriptase / metabolism*
  • HIV-1 / drug effects
  • Humans
  • Naphthalenes / chemical synthesis*
  • Naphthalenes / pharmacology
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology
  • Uracil / analogs & derivatives*
  • Uracil / chemical synthesis*
  • Uracil / pharmacology

Substances

  • Alkenes
  • Alkynes
  • Anti-HIV Agents
  • Naphthalenes
  • Reverse Transcriptase Inhibitors
  • Uracil
  • HIV Reverse Transcriptase