RELATIONSHIP BETWEEN STRUCTURE AND BIOAVAILABILITY IN A SERIES OF HYDROXAMATE BASED METALLOPROTEASE INHIBITORS

Pharmacokinetic parameters for a series of C-terminally modified hydro xamate dipeptides were evaluated by in vitro and in vivo models. The p resence of a tertiary base at the C-terminus significantly reduced bil iary excretion and increased plasma half-life. Moreover, introduction of a thioether functionality produced a more favorable pharmacokinetic profile compared to the corresponding oxo- and aza-analogs.