The synthesis, antiviral, cytostatic and cytotoxic evaluation of a new series of acyclonucleotide analogues with a 1,2,3-triazole linker

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• 作者：Iwona E. G艂owacka ; Jan Balzarini ; Andrzej E. Wr贸blewski
• 关键词：Aziodophosphonates ; Acyclonucleotides ; 1 ; 2 ; 3-Triazoles ; Synthesis ; Antiviral ; Cytostatic
• 刊名：European Journal of Medicinal Chemistry
• 出版年：December, 2013
• 年：2013
• 卷：70
• 期：Complete
• 页码：703-722
• 全文大小：979 K

文摘

The efficient synthesis of a new series of acyclonucleotide analogues with a 1,2,3-triazole linker is described starting from diethyl azidomethyl-, 2-azidoethyl-, 3-azidopropyl-, 4-azidobutyl-, 2-azido-1-hydroxyethyl-, 3-azido-2-hydroxypropyl- and 3-azido-1-hydroxypropylphosphonates and selected alkynes under microwave irradiation. Several O,O-diethylphosphonate acyclonucleotides were transformed into the respective phosphonic acids. All compounds were evaluated in聽vitro for activity against a broad variety of DNA and RNA viruses and cytostatic activity against murine leukaemia L1210, human T-lymphocyte CEM and human cervix carcinoma HeLa cells. Acyclonucleotide 22e exhibited activity against both herpes simplex viruses (HSV-1, HSV-2) in HEL cell cultures (EC₅₀聽=聽17聽渭M) and feline herpes virus (EC₅₀聽=聽24聽渭M) in CRFK cell cultures, while compounds 20k, 21k, 22k and 23k preferentially inhibited proliferation of human T-lymphocyte CEM cells at IC₅₀ in the 2.8-12聽渭M range.