Departmental Papers (CBE)

Document Type

Journal Article

Date of this Version

January 2008


Library samples containing 2,5-disubstituted oxadiazoles were identified as potent hits in a high throughput screen (HTS) of the NIH Molecular Libraries Small Molecule Repository (MLSMR) directed at discovering inhibitors of cathepsin L. However, when synthesized in pure form, the putative actives were found to be devoid of biological activity. Analyses by LC–MS of original library samples indicated the presence of a number of impurities, in addition to the oxadiazoles. Synthesis and bioassay of the probable impurities led to the identification of a thiocarbazate that likely originated via ring opening of the oxadiazole. Previously unknown, thiocarbazates (-)-11 and (-)-12 were independently synthesized as single enantiomers and found to inhibit cathepsin 20 L in the low nanomolar range.


Postprint version. Published in Bioorganic and Medicinal Chemistry Letters, Volume 18, Issue 1, January 2008, pages 210-214.
Publisher URL:


thiocarbazate; cathepsin L inhibitor; cysteine protease inhibitor; MLSCN



Date Posted: 09 April 2008

This document has been peer reviewed.