Synthesis and evaluation of 4-substituted benzylamine derivatives as β-tryptase inhibitors

Since β-tryptase is considered a critical mediator of asthma, potent tryptase inhibitors may be useful as new agents for the treatment of asthma. We investigated 4-substituted benzylamine derivatives and obtained M58539 (15h) as a potent inhibitor of β-tryptase (IC50 = 5.0 nM) with high selectivity against other serine proteases, low molecular weight, c log P value less than 5, lack of amidino and guanidino groups, and independence of Zn2+ ion.

Graphical abstractSynthesis and structure–activity relationships of β-tryptase inhibitors are described.Figure optionsDownload full-size imageDownload as PowerPoint slide