Cathepsin L inhibitors and probes comprising vinyl sulfonate moiety and methods of using same

摘要

Human cathepsin L inhibitors and probes containing a vinyl sulfonate ester moiety are described. The inhibitors are highly potent (low nM affinity), selective, and cell permeable, and can inhibit ultra-low concentration of active cathepsin L. The developed probes are highly sensitive and can detect an ultra-low amount of probe-labeled active cathespin L.

主权项

1. A method for inhibiting cathepsin L or probing the activity of cathepsin L, the method comprising steps of:
exposing a biological cell to a compound of Formula (A) or a pharmaceutically acceptable solvate, hydrate, salt or N-oxide thereof: wherein,R1 is selected from the group consisting of Br, Cl, I, an aryl, CO2CH3, CN and NO2;each R2 is independently selected from the group consisting of F, CF3, aryl and methyl;each R3 is independently selected from the group consisting of F, CF3 aryl and methyl;R4 is selected from the group consisting of H, CCH and N3;R5 is selected from the group consisting of methyl, ethyl and propyl;R6 is an aryl;n is 0, 1 or 2m is 0, 1 or 2.