Antiviral and antineoplastic activities of pyrimidine arabinosyl nucleosides and their 5'-amino derivatives

Journal of Medicinal Chemistry
1979.0

Abstract

Since 1-(5-amino-5-deoxy-β-D-erythro-pentofuranosyl)-5-iodouracil (AIU, AIdUrd) inhibits the replication of herpes simplex virus type 1 (HSV-1) with little or no host cell toxicity and arabinosyl nucleosides, such as β-D-arabinofuranosylthymine (ara-T, aThy), 9-β-D-arabinofuranosyladenine (ara-A), and 1-β-D-arabinofuranosylcytosine (ara-C), have antiviral and/or cytostatic activity, the synthesis of the corresponding arabinonucleosides with an amino substituent in the 5' position in substitution of the 5'-hydroxyl moiety was undertaken. The objective was the preparation of more potent antiviral compounds with retention of the selective antiviral activity associated with the 5'-amino moiety. The synthesis of 1-(5-amino-5-deoxy-β-D-arabinofuranosyl)uracil, -thymine, -bromouracil and -iodouracil analogues is described. The effect of these 5'-aminoarabinonucleoside analogues and their precursors on HSV-1, sarcoma 180 (S-180), and L1210 cells in culture, as well as their ability to inhibit the phosphorylation of thymidine by HSV-1 encoded pyrimidine 2'-deoxyribonucleoside kinase, is compared with that of the respective parent compounds. None of the 5'-azido- or 5'-aminoarabinosyl nucleoside analogues exhibited significant cytotoxic or antiviral activity. aThy and the corresponding halogen-containing analogues were found to have a marked cytostatic effect on S-180 and L1210 cells in culture, as well as potent antiviral activity against HSV-1.

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