Synthesis and Anti-HIV-1 Evaluation of Some Novel MC-1220 Analogs as Non-Nucleoside Reverse Transcriptase Inhibitors

Arch Pharm (Weinheim). 2016 May;349(5):363-72. doi: 10.1002/ardp.201600008. Epub 2016 Mar 21.

Abstract

Some novel MC-1220 analogs were synthesized by condensation of 4,6-dichloro-N-methylpyrimidin-2-amine derivatives (1a,b and 15) and/or 4-chloro-6-methoxy-N,N,5-trimethylpyrimidin-2-amine (2a) with the sodium salt of 2,6-difluorophenylacetonitrile followed by treatment with aqueous sodium hydroxide in methanol, alkylation, reduction, halogenation, and/or acidic hydrolysis. All synthesized compounds were evaluated for their activity against HIV-1. The most active compound in this study was compound 7, which showed activity against HIV-1 comparable to that of MC-1220. The only difference in structure between compound 7 and MC-1220 is a fluoro atom instead of a CH3 group.

Keywords: 2,6-Difluorobenzyl cyanide; 4,6-Dichloro-N,N-dimethylpyrimidin-2-amine; HIV-1; MC-1220 analogs; Non-nucleoside reverse transcriptase inhibitor (NNRTI).

MeSH terms

  • Anti-HIV Agents / chemical synthesis*
  • Anti-HIV Agents / pharmacology*
  • Cell Line
  • Cells, Cultured
  • Fluorobenzenes / pharmacology*
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV-1 / drug effects
  • Microbial Sensitivity Tests
  • Models, Molecular
  • Pyrimidinones / pharmacology*
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • 6-(1-(2,6-difluorophenyl)ethyl)-2-(dimethylamino)-5-methylpyrimidin-4(3H)-one
  • Anti-HIV Agents
  • Fluorobenzenes
  • Pyrimidinones
  • Reverse Transcriptase Inhibitors
  • HIV Reverse Transcriptase