Acta Pharm. 57 (2007) 379-393

full paper

Original research paper

 

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

 

YASEEN A. AL-SOUD, NAJIM A. AL-MASOUDI, HAMED GH. HASSAN, ERIK DE CLERCQ and CHRISTOPHE PANNECOUQUE

Najim.Al-Masoudi@gmx.de

Department of Chemistry, College of Science, University of Al al-Bayt, Al-Mafraq, Jordan

Fachbereich Chemie, Universität Konstanz, Postfach 5560, D-78457 Konstanz, Germany (formerly)

College of Science, Department of Chemistry, University of Sulaimany, Iraq

Rega Institute for Medical Research, Katholieke Universiteit Leuven, B-3000 Leuven, Belgium

Accepted July 27, 2007

 

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 new non-nucleoside reverse transcriptase inhibitors (NNRTIs). The newly synthesized compounds were assayed against HIV-1 and HIV-2 in MT-4 cells. Compound 2 showed inhibition of HIV-1 (EC50 0.45 µg mL-1) and HIV-2 (0.50 µg mL-1), while 9 showed inhibition of HIV-1 (EC50 2.48 µg mL-1, SI = 4).

 

Keywords: anti-HIV activity, 4-nitroimidazoles, NNRTIs, piperazine