THE CHARACTERIZATION OF POTENT NOVEL WARFARIN ANALOGS

Racemic sodium warfarin, Coumadin,(R) is widely used in the prevention of thromboembolic disease. The present study was undertaken to charac terize three novel classes of warfarin analogs, and to compare them wi th the warfarin enantiomers. All three classes of compounds inhibit vi tamin K epoxide reductase, the enzyme inhibited by racemic warfarin. T he alcohol and the ester analogs have reduced protein binding compared with R-(+)-warfarin(1). The ester and the fluoro-derivatives have sim ilar in vivo anticoagulant activity in the rat to that of S-(-)-warfar in(1). Thus, it is possible to synthesize novel warfarin analogs that differ from racemic warfarin or its enantiomers in certain selected pr operties. (C) 1997 Elsevier Science Ltd.