1043899-47-3Relevant academic research and scientific papers
Design, synthesis, and evaluation of inhibitors of cathepsin L: Exploiting a unique thiocarbazate chemotype
Myers, Michael C.,Shah, Parag P.,Beavers, Mary Pat,Napper, Andrew D.,Diamond, Scott L.,Smith III, Amos B.,Huryn, Donna M.
, p. 3646 - 3651 (2008)
Recently, we identified a thiocarbazate that exhibits potent inhibitory activity against human cathepsin L. Since this structure represents a novel chemotype with potential for activity against the entire cysteine protease family, we designed, synthesized, and assayed a series of analogs to probe the mechanism of action, as well as the structural requirements for cathepsin L activity. Molecular docking studies using coordinates of a papain-inhibitor complex as a model for cathepsin L provided useful insights.
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.
