Synthesis, antiviral, cytotoxic and cytostatic evaluation of N1-(Phosphonoalkyl)uracil derivatives

Article abstract of DOI:10.1007/s00706-016-1701-2

A series of N¹-(phosphonoalkyl)uracils was prepared in a two-step reaction sequence from x- aminoalkylphosphonates and (E)-3-ethoxyacryloyl isocyanate followed by the uracil ring closure. Under standard conditions (NCS; NBS; I₂/CAN) all N¹-(phosphonoalkyl)uracils were transformed into the respective 5-halogeno derivatives to be later benzoylated at N3. All compounds were evaluated in vitro for activity against a broad variety of DNA and RNA viruses. One compound was slightly active against human cytomegalovirus in HEL cell cultures (EC₅₀ = 45 μM) while another showed weak activity against varicella-zoster virus (TK⁺ VZV strain OKA and TK^- VZV strain 07-1) with EC₅₀ = 43 and 53 μM, respectively. In addition, several compounds exhibited noticeable inhibitory effects on the proliferation of human cervical carcinoma cells (HeLa) at a concentration lower than 200 μM.