Synthesis and anti-HIV activity of 2-naphthyl substituted DAPY analogues as non-nucleoside reverse transcriptase inhibitors

Bioorg Med Chem. 2010 Jul 1;18(13):4601-5. doi: 10.1016/j.bmc.2010.05.036. Epub 2010 May 20.

Abstract

Nine newly 6-cyano-2-naphthyl substituted diarylpyrimidines (DAPY) were synthesized as non-nucleoside reverse transcriptase inhibitors on the basis of our previous work. The antiviral and cytotoxicity evaluation indicated that these compounds displayed strong activity against wild-type HIV-1 at nanomolar concentrations with selectivity index SI greater than 23 779. The most active compounds 3c and 3e exhibited activity against the double mutant (103N+181C) strains at an EC₅₀ of 0.16 and 0.15 μM, and were more activity than that of efavirenz.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkynes
  • Anti-HIV Agents / chemical synthesis
  • Anti-HIV Agents / chemistry*
  • Anti-HIV Agents / toxicity
  • Benzoxazines / pharmacology
  • Binding Sites
  • Cell Line
  • Computer Simulation
  • Cyclopropanes
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / enzymology*
  • Humans
  • Naphthols / chemical synthesis
  • Naphthols / chemistry*
  • Naphthols / toxicity
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry*
  • Pyrimidines / toxicity
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / toxicity

Substances

  • 5-chloro-6-(2-(4-cyanophenylamino)pyrimidin-4-yloxy)-7-methoxy-2-naphthonitrile
  • 6-(2-(4-cyanophenylamino)pyrimidin-4-yloxy)-5,7-dimethoxy-2-naphthonitrile
  • Alkynes
  • Anti-HIV Agents
  • Benzoxazines
  • Cyclopropanes
  • Naphthols
  • Pyrimidines
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase
  • efavirenz