Design, synthesis, and biological activity of potent and selective inhibitors of mast cell tryptase.

A new series of novel mast cell tryptase inhibitors is reported, which features the use of an indole structure as the hydrophobic substituent on a m-benzylaminepiperidine template. The best members of this series display good in vitro activity and excellent selectivity against other serine proteases.

Novel pyrazinone inhibitors of mast cell tryptase: synthesis and SAR evaluation.

In this manuscript, the synthesis and SAR evaluation of a novel pyrazinone class of tryptase inhibitors is described. Chemical optimization of the P1 and P4 groups led to the identification of 7p (K(i)=93 nM) as a potent inhibitor of mast cell tryptase.

Design of bivalent ligands using hydrogen bond linkers: synthesis and evaluation of inhibitors for human beta-tryptase.

We exploit the concept of using hydrogen bonds to link multiple ligands for maintaining simultaneous interactions with polyvalent binding sites. This approach is demonstrated by the syntheses and evaluation of pseudo-bivalent ligands as potent inhibitors of human beta-tryptase.