Acetylenic nucleosides. 4. 1-β-D-arabinofuranosyl-5-ethynylcytosine. Improved synthesis and evaluation of biochemical and antiviral properties

Article abstract of DOI:10.1021/jm00394a039

5-Ethynyl-1-β-D-arabinofuranosylcytosine (EAC) was prepared from 1-(2,3,5-tri-O-acetyl-β-D-arabinofuranosyl)cytosine by iodination followed by coupling with (trimethylsilyl)acetylene and deblocking. At 50 μM, EAC was found to inhibit the in vitro replication of herpes simplex virus type 1 and type 2 by >99%. EAC also showed activity against a strain of HSV-1 resistant to (E)-5-(2-bromovinyl)-2'-deoxyuridine which has an alteration of the virus-induced thymidine kinase (TK).. At 100 μM, EAC did not inhibit the in vitro growth of leukemia L1210 and HeLa cells. EAC was resistant to the action of dCR-CR deaminase, its rate of deamination being approximately 2% that of dCR. The compound was a poor substitute for dCR kinase, but it was phosphorylated by HSV-1- and HSV-2-induced TKs at 50% and 30%, respectively, the rate of thymidine.