1194046-54-2Relevant academic research and scientific papers
Design, synthesis and biological evaluation of a library of thiocarbazates and their activity as cysteine protease inhibitors
Liu, Zhuqing,Myers, Michael C.,Shah, Parag P.,Beavers, Mary Pat,Benedetti, Phillip A.,Diamond, Scott L.,Smith, Amos B.,Huryn, Donna M.
scheme or table, p. 337 - 351 (2010/09/04)
Recently, we identified a novel class of potent cathepsin L inhibitors, characterized by a thiocarbazate warhead. Given the potential of these compounds to inhibit other cysteine proteases, we designed and synthesized a library of thiocarbazates containing diversity elements at three positions. Biological characterization of this library for activity against a panel of proteases indicated a significant preference for members of the papain family of cysteine proteases over serine, metallo-, and certain classes of cysteine proteases, such as caspases. Several potent inhibitors of cathepsin L and S were identified. The SAR data were employed in docking studies in an effort to understand the structural elements required for cathepsin S inhibition. This study provides the basis for the design of highly potent and selective inhibitors of the papain family of cysteine proteases.
