Abstract
| - A new procedure for the synthesis of cyclohexanone-based inhibitors of serine proteases is reported.In this procedure the reactive ketone functionality is carried through the synthesis in masked formas a TBDMS-protected alcohol. Deprotection followed by oxidation of the alcohol generates thefinal form of the inhibitor. Two new inhibitors, which interact with the S1−S3 and S2‘ subsites ofplasmin, are synthesized using this procedure. Inhibitors 1 and 2 have IC50 values against plasminof 20 and 24 μM, respectively. The inhibition studies show that cooperative binding of inhibitors inthe S1 and S2 subsites of plasmin is important for determining inhibitor selectivity.
|