Pyrazole-based cathepsin S inhibitors with arylalkynes as P1 binding elements

Bioorganic and Medicinal Chemistry Letters

Volumn 19, Issue 21, 2009, Pages 6131-6134

  Ameriks, Michael K ^a   Axe, Frank U ^a   Bembenek, Scott D ^a   Edwards, James P ^a   Gu, Yin ^a   Karlsson, Lars ^a   Randal, Mike ^b   Sun, Siquan ^a   Thurmond, Robin L ^a   Zhu, Jian ^a  

^a JOHNSON AND JOHNSON PHARMACEUTICAL RESEARCH AND DEVELOPMENT   (United States)

^b Sunesis Pharmaceuticals Inc   (United States)

Author keywords

Alkyne; Cathepsin; Protease; X ray crystallography

Indexed keywords

ALKYNE DERIVATIVE; CATHEPSIN S; CATHEPSIN S INHIBITOR; CHAPERONE; CYSTEINE; SERINE;

ANTIGEN PRESENTATION; ARTICLE; CONTROLLED STUDY; DRUG BINDING SITE; DRUG CONFORMATION; DRUG DESIGN; HUMAN; HUMAN CELL; HYDROGEN BOND; IC 50; MAJOR HISTOCOMPATIBILITY COMPLEX; MOUSE; NONHUMAN; PHARMACOPHORE; RAT; SONOGASHIRA REACTION; STRUCTURE ACTIVITY RELATION; SUBSTITUTION REACTION; X RAY ANALYSIS; X RAY CRYSTALLOGRAPHY;

AMINO ACID SUBSTITUTION; BINDING SITES; CATHEPSINS; CRYSTALLOGRAPHY, X-RAY; DRUG DESIGN; HUMANS; MUTAGENESIS, SITE-DIRECTED; PROTEASE INHIBITORS; PYRAZOLES; PYRIDINES; RECOMBINANT PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 71749093965     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.bmcl.2009.09.014     Document Type: Article

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33. The crystal structure of compound 1 could not be uploaded into the PDB because structure factors were not provided by Sunesis Pharmaceuticals, presumably because they were note required for submission into the PDB at the time this structure was solved (2003).
34. The electron density for the methyl group in oxamide 1 could not be observed, so it is not clear which oxygen of the oxamide forms a H-bond with Asn161.