290817-22-0Relevant academic research and scientific papers
Arylamine based cathepsin K inhibitors: Investigating P3 heterocyclic substituents
Shinozuka, Tsuyoshi,Shimada, Kousei,Matsui, Satoshi,Yamane, Takahiro,Ama, Mayumi,Fukuda, Takeshi,Taki, Motohiko,Takeda, Yuko,Otsuka, Eri,Yamato, Michiko,Naito, Satoru
, p. 6807 - 6819 (2007/10/03)
A modification of novel cathepsin K inhibitors I was carried out. The structural design was aimed at reducing the lipophilic character of compounds I for obtaining better pharmacokinetic profiles. This modification afforded several less lipophilic compoun
Design and synthesis of dipeptide nitriles as reversible and potent cathepsin S inhibitors
Ward, Yancey D.,Thomson, David S.,Frye, Leah L.,Cywin, Charles L.,Morwick, Tina,Emmanuel, Michel J.,Zindell, Renée,McNeil, Daniel,Bekkali, Younes,Giradot, Marc,Hrapchak, Matt,DeTuri, Molly,Crane, Kathy,White, Della,Pav, Susan,Wang, Yong,Hao, Ming-Hong,Grygon, Christine A.,Labadia, Mark E.,Freeman, Dorothy M.,Davidson, Walter,Hopkins, Jerry L.,Brown, Maryanne L.,Spero, Denice M.
, p. 5471 - 5482 (2007/10/03)
The specificity of the immune response relies on processing of foreign proteins and presentation of antigenic peptides at the cell surface. Inhibition of antigen presentation, and the subsequent activation of T-cells, should, in theory, modulate the immune response. The cysteine protease Cathepsin S performs a fundamental step in antigen presentation and therefore represents an attractive target for inhibition. Herein, we report a series of potent and reversible Cathepsin S inhibitors based on dipeptide nitriles. These inhibitors show nanomolar inhibition of the target enzyme as well as cellular potency in a human B cell line. The first X-ray crystal structure of a reversible inhibitor cocrystallized with Cathepsin S is also reported.
