Nitroimidazoles. V. Synthesis and anti-HIV evaluation of new 5-substituted piperazinyl-4-nitroimidazole derivatives

Acta Pharm. 2007 Dec;57(4):379-93. doi: 10.2478/v10007-007-0031-7.

Abstract

A series of 2-alkylthio-1-[4-(1-benzyl-2-ethyl-4-nitro-1H- -imidazol-5-yl)-piperazin-1-yl]ethanones (3-9) and alkyl-[4-(1-benzyl-2-ethyl-4-nitro-1H-imidazol-5-yl)-piperazin-1-yl)ketones (11-20) as well as the indole analogue 22 were synthesized from 4-nitro-5-piperazinyl imidazole derivative 1, with the aim to develop newly non-nucleoside reverse transcriptase inhibitors (NNRTIs). The newly synthesized compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. Compound 4 showed inhibition of HIV-1 (EC50 0.45 microg mL-1) and HIV-2 (0.50 microg mL-1), while 11 showed inhibition of HIV-1 (EC50 2.48 microg mL-1, SI = 4).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-HIV Agents* / chemical synthesis
  • Anti-HIV Agents* / pharmacology
  • Cell Line, Tumor
  • Dose-Response Relationship, Drug
  • Drug Resistance, Multiple, Viral
  • HIV Reverse Transcriptase / antagonists & inhibitors*
  • HIV Reverse Transcriptase / metabolism
  • HIV-1 / drug effects*
  • HIV-1 / enzymology
  • HIV-1 / growth & development
  • HIV-2 / drug effects*
  • HIV-2 / enzymology
  • HIV-2 / growth & development
  • Humans
  • Molecular Structure
  • Nitroimidazoles* / chemical synthesis
  • Nitroimidazoles* / pharmacology
  • Reverse Transcriptase Inhibitors* / chemical synthesis
  • Reverse Transcriptase Inhibitors* / pharmacology
  • Structure-Activity Relationship

Substances

  • Anti-HIV Agents
  • Nitroimidazoles
  • Reverse Transcriptase Inhibitors
  • reverse transcriptase, Human immunodeficiency virus 1
  • reverse transcriptase, Human immunodeficiency virus 2
  • HIV Reverse Transcriptase