Nitroimidazoles, Part 2

Abstract A series of 5‐alkylamino and 5‐alkylsulfanyl derivatives of 1‐aryl‐2‐alkyl‐4‐nitro‐1 H ‐imidazoles 12 – 21, 31 , and 34 were synthesized by a simple method with the aim to develop novel HIV non‐nucleoside reverse transcriptase inhibitors (NNRTIs). All the new compounds were tested against HIV‐1 and HIV‐2 in MT‐4 cells. Compound 21 , with an arylsulfanyl group at C(5) of the 4‐nitro‐1 H ‐imidazole backbone showed an EC 50 value of 0.22 μg/ml against HIV‐1 with a therapeutic index of 13. This means that compound 21 was cytotoxic to MT‐4 cells at a CC 50 value of 2.57 μg/ml; also compounds 8, 22 – 25, 28 , and 29 were cytotoxic to MT‐4 cells within the 0.4–4 μg/ml concentration range. Compounds 8 , and 12 – 21 were evaluated, as a rule, but found inactive at non‐toxic concentrations against hepatitis C virus, herpes simplex type 1 and 2, cytomegalovirus (CMV), varicella‐zoster virus (VZV), vaccinia virus, and vesicular stomatitis virus, and a number of other viruses. Yet, the therapeutic index of compounds 17 and 21 for CMV and VZV approached the tenfold cut‐off point. Compounds 8 and 21 exhibited some cytostatic activity against leukemia and melanoma cell lines.