Synthesis of (E)-5-(3,3,3-trifluoro-1-propenyl)-2'-deoxyuridine and related analogs: potent and unusually selective antiviral activity of (E)-5-(3,3,3-trifluoro-1-propenyl)-2'-deoxyridine against herpes simplex virus type 1

Abstract

Syntheses of (E)-5-(3,3,3-trifluoro-1-propenyl)-2''-deoxyuridine (TFPe-dUrd), 5-(3,3,3-trifluoro-1-propyl)-2''-deoxyuridine, 5-(3,3,3-trifluoro-1-methoxy-1-propyl)-2''-deoxyuridine and 5-(3,3,3-trifluoro-1-hydroxy-1-propyl)-2''-deoxyuridine from 5-chloromercuri-2''-deoxyuridine are described. The antiviral activity of TFPe-dUrd was determined in cell culture against herpes simplex virus type 1, herpes simplex virus type 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 virus yield at 0.03 .mu.g/ml (0.09 .mu.M); L-1210 [mouse leukemia] cell growth was inhibited by 50% only at 290 .mu.g/ml. Isopycnic centrifugation of 32P-labeled DNA indicated that if 0.5 or 2 .mu.M TFPe-dUrd was present for 0-6 h postinfection, viral DNA synthesis was reduced by .apprx. 50 and 85%, respectively; concomitantly, a new DNA band appeared at lower density than normal cellular or viral DNA.