The substrate activity screening (SAS) method, a substrate-based fragment identification and optimization method for the development of enzyme inhibitors, was previously applied to cathepsin S to obtain a novel (2-arylphenoxy) acetaldehyde inhibitor, 2, with a 0.49 μM K i value (Wood, WJL; Patterson, AW; Tsuruoka, H.; Jain, RK; Ellman, JAJ Am. Chem. Soc. 2005, 127, 15521-15527). In this paper we disclose the X-ray structure of a complex ...
