Synthesis of (E)-5-(3,3,3-Trifluoro-1-propenyl)-2'-deoxyuridine and Related Analogues: Potent and Unusually Selective Antiviral Activity of (E)-5-(3,3,3-Trifluoro-1-propenyl)-2'-deoxyuridine against Herpes Simplex Virus Type 1

Article abstract of DOI:10.1021/jm00369a009

Syntheses of (E)-5-(3,3,3-trifluoro-1-propenyl)-2'-deoxyuridine (TFPe-dUrd) (1), 5-(3,3,3-trifluoro-1-propyl)-2'-deoxyuridine (11), 5-(3,3,3-trifluoro-1-methoxy-1-propyl)-2'-deoxyuridine (8), and 5-(3,3,3-trifluoro-1-hydroxy-1-propyl)-2'-deoxyuridine (10) from 5-chloromercuri-2'-deoxyuridine are described.The antiviral activity of TFPe-dUrd was determined in cell culture against herpes simplex virus type 1 (HSV-1), herpes simplex virus type 2 (HSV-2), and vaccinia virus and compared concurrently with 5-(1-propenyl)-2'-deoxyuridine, 5-(2-bromovinyl)-2'-deoxyuridine,5-iodo-2'-deoxyuridine, and 5-(trifluoromethyl)-2'-deoxyuridine.TFPe-dUrd demonstrated a potent and unusually selective activity against HSV-1, with a 2-log reduction in virud yield at 0.03 μg/mL (0.09 μM); L-1210 cell growth was inhibited by 50percent only at 290 μg/mL.Isopycnic centrifugation of 32P-labeled DNA indicated that if 0.5 or 2 μM TFP3-dUrd was present for 0-6 h postinfection, viral DNA synthesis was reduced by ca. 50 and 85percent, respectively; concomitantly, a new DNA band appeared at lower density than normal cellular or viral DNA.