The design and synthesis of novel α-ketoamide-based p38 MAP kinase inhibitors

Autor:	Eric Erb, Russell Dahl, Jan Lundström, Robert K. P. Sullivan, Chau-Dung Chang, Erik Boman, Edward Roberts, Antonio Garrido Montalban, Andrew Gibbs, Justin T. Ernst, Jeffrey Kahl, Hiroshi Nakanishi, Nancy G. J. Delaet, Eddine Saiah, Linda Kessler, Stephen E. Miller, Susana Conde Ceide, Christopher J. Larson, David Dalesandro, Zhijun Wang
Rok vydání:	2008
Předmět:	Lipopolysaccharides Models Molecular Protein Conformation Stereochemistry Clinical Biochemistry Allosteric regulation Pharmaceutical Science Plasma protein binding Crystallography X-Ray p38 Mitogen-Activated Protein Kinases Biochemistry Monocytes Structure-Activity Relationship Adenosine Triphosphate In vivo Drug Discovery Animals Humans Structure–activity relationship Phosphorylation Binding site Protein Kinase Inhibitors Molecular Biology Cells Cultured ADME chemistry.chemical_classification Binding Sites Molecular Structure Tumor Necrosis Factor-alpha Organic Chemistry Amides In vitro Rats Enzyme chemistry Drug Design Molecular Medicine Allosteric Site Protein Binding
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 18:1772-1777
ISSN:	0960-894X
Popis:	We have identified a novel series of potent p38 MAP kinase inhibitors through structure-based design which due to their extended molecular architecture bind, in addition to the ATP site, to an allosteric pocket. In vitro ADME and in vivo PK studies show these compounds to have drug-like characteristics which could result in the development of an oral treatment for inflammatory conditions.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9e1a60a704c68cbb7566ac6bd4230098 https://doi.org/10.1016/j.bmcl.2008.02.033 Zobrazit plný text záznamu Full Text from ScienceDirect