Nitroimidazoles, part 4: Synthesis and anti‐HIV activity of new 5‐alkylsulfanyl and 5‐(4′‐arylsulfonyl)piperazinyl‐4‐nitroimidazole derivatives

Abstract The development of new HIV nonnucleoside reverse transcriptase inhibitors (NNRTIs) offers the possibility of generating structures of increased potency. On this basis, a series of 5‐alkylsulfanyl and 5‐(4′‐arylsulfonyl)piperazine derivatives of 1‐phenyl‐2‐alkyl‐4‐nitroimidazoles 5–21 was synthesized with the aim to develop new NNRTIs. The new synthesized compounds were assayed against HIV‐1 and HIV‐2 in MT‐4 cells. Compounds 9 and 13 , with an alkylsulfanyl group at C‐5 of the 4‐nitroimidazole backbone, showed inhibition of HIV‐1 with EC 50 4.04 μg/mL and 2.37 μg/mL, and therapeutic indexes (SI) of 17 and 13, respectively. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:333–340, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20301