Synthesis, radiosynthesis, in vitro and first in vivo evaluation of a new matrix metalloproteinase inhibitor based on γ-fluorinated α-sulfonylaminohydroxamic acid.

(Radio)synthesis of a CGS based γ-fluorinated MMP inhibitor was successfully accomplished. The (S)-enantiomer, which normally shows no biological activity, also exhibited high MMP inhibition potencies, which may be attributed to additional interactions of fluorine with enzyme's active site. Despite higher hydrophilicity no significant differences in the clearance characteristics compared to non-fluorinated MMPIs was observed. Metabolically stabilizing effect of the fluorine was not monitored in vivo in wild type mice.