Synthesis and biological properties of (E)-5-(2-[82Br]bromovinyl)-1-(2-deoxy-2-fluoro-β-D-ribofuranosyl)uracil ([82Br]BVFRU)

(E)-5-(2-Bromovinyl)-1-(2-deoxy-2-fluoro-β-D-ribofuranosyl) uracil (BVFRU) was synthesized in 24% yield by reacting (E)-5-(2-carboxyvinyl)-1-(2-deoxy-2-fluoro-β-D-ribofuranosyl)uracil (CVFRU) with NH4Br in the presence of chloramine-T. [82Br]BVFRU was prepared in 14.5% radiochemical yield, with a specific activity of 58 MBq mmol-1, by a similar reaction of CVFRU with ammonium [82Br]bromide. BVFRU is equipotent to iodovinyldeoxyuridine (IVDU) and iodovinyl-2'-fluorodeoxyuridine (IVFRU) (MIC50 = 0.1-0.01 μg mL-1) against herpes simplex virus which encodes for thymidine kinase (HSV-1 TK+), and has a partition coefficient similar to that of IVDU and IVFRU (log P = 0.72 vs 1.6 and 1.21, respectively). BVFRU has an inhibition constant (Ki) of 0.044 for the nitrobenzylthioinosine (NBMPR)-sensitive transport of thymidine across the murine erythrocyte membrane. These data suggest that BVFRU is similar to BVDU in antiviral potency and transport characteristics; it is proposed that ease of synthesis and resistance to metabolic degradation make radiolabelled BVFRU a superior candidate for in vivo diagnostic studies of HSE. (author)