5-Substituted uracil arabinonucleosides as potential antiviral agents

Article abstract of DOI:10.1021/jm00189a020

Four 5-substituted analogues of 1 (β D arabinofuranosyl)uracil were prepared and evaluated as antiviral agents. 1 (β D Arabinofuranosyl) 5 (propynyloxy)uracil (5) was prepared by the propargyl bromide alkylation of 1 (β D r584w92 =water 5 hydroxyuracil (6) which was synthesized by reaction of 1 (β D arabinofuranosyl)uracil with bromine watery pyridine. Compound 6 could also be prepared by bromine water pyridine treatment of 1 (2,3,5 tri O acetyl β D arabinofuranosyl)uracil, followed by removal of the acetyl groups by NH₃-CH₃OH. 1 (β D Arabinofuranosyl) 5 cyanouracil (4) was synthesized by basic cleavage of O² 2' anhydro 5 cyanouridine which was prepared by reaction of 5 cyanouridine with diphenyl carbonate in hexamethylphosphoramide. 1 (β D Arabinofuranosyl) 5 nitrouracil (1) was obtained by nitration of 2',3',5' tri O (3,5 dinitrobenzoyl)uridine (2) with fuming HNO₃-H₂SO₄, followed by removal of the protecting groups with NaOEt-EtOH. Compounds 1, 4, and 6 were devoid of significant antiviral activity against herpes simplex (type 1) virus, vaccinia virus, and vesicular stomatitis virus in primary rabbit kidney cell cultures and human skin fibroblasts. The propynyloxy analogue, 5, showed an anti herpes virus activity comparable to 1 (β D arabinofuranosyl)uracil but was substantially less active than 1 (β D arabinofuranosyl)thymine.