Design of novel, potent, and selective human β-tryptase inhibitors based on α-keto-[1,2,4]-oxadiazoles

A series of novel α-keto-[1,2,4]-oxadiazoles has been synthesized as human tryptase inhibitors for evaluation as a new class of anti-asthmatic agent. The inhibitor design is focused on using a prime-side hydrophobic pocket and the S2 pocket of β-tryptase to achieve inhibition potency and selectivity over other serine proteases.

Graphical abstractA series of novel α-keto-[1,2,4]-oxadiazoles has been synthesized as human tryptase inhibitors for evaluation as a new class of anti-asthmatic agent. The inhibitor design is focused on using a prime-side hydrophobic pocket and the S2 pocket of β-tryptase to achieve inhibition potency and selectivity over other serine proteases.Figure optionsDownload full-size imageDownload as PowerPoint slide