Synthesis, antiviral, cytotoxic and cytostatic evaluation of N 1-(phosphonoalkyl)uracil derivatives

Abstract

A series of N 1 -(phosphonoalkyl)uracils was prepared in a two-step reaction sequence from xaminoalkylphosphonates and (E)-3-ethoxyacryloyl isocyanate followed by the uracil ring closure. Under standard conditions (NCS; NBS; I 2 /CAN) all N 1 -(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 (EC 50 = 45 lM) while another showed weak activity against varicella-zoster virus (TK ? VZV strain OKA and TK -VZV strain 07-1) with EC 50 = 43 and 53 lM, respectively. In addition, several compounds exhibited noticeable inhibitory effects on the proliferation of human cervical carcinoma cells (HeLa) at a concentration lower than 200 lM. Graphical abstract

Carbohydrates as potentially versatile core subcarriers for multivalent immunogens

“…Structure of the by-product 6 was determined on the basis of the spectral data (NMR, MS) and the literature precedence. 36–38 The same holds for deduction of structures of compounds 9, 15 , and 18 described below. Because the proportion of side product 6 was unacceptably high, more favourable conditions for azide reduction were sought.…”

Uracil: A Pharmacophore with Diverse Biological Potential

“…Wen et al [67] Tokarska et al [71] synthesised a series of N 1 -(phosphonoalkyl)uracils of the type 138 a-b. The reaction involved the treatment of uracil phosphonates 137 a-b with benzoyl chloride to yield N 3 -benzoyluracils 138 a-b (Scheme 36).…”