Indole RSK inhibitors. Part 2: Optimization of cell potency and kinase selectivity

Autor:	Mohammed A. Kashem, Stanley Kugler, Lida Soleymanzadeh, Yunlong Zhang, Jeffery B. Madwed, Xin Guo, Kirrane Thomas M, Roger J. Snow, Alan David Swinamer, Jennifer Burke, Margaret M. O’Neill, Stephen J. Boyer
Rok vydání:	2012
Předmět:	Indoles Nitrogen Chemistry Pharmaceutical Clinical Biochemistry Drug Evaluation Preclinical Molecular Conformation Pharmaceutical Science Crystallography X-Ray Ribosomal Protein S6 Kinases 90-kDa Biochemistry Ribosomal s6 kinase Inhibitory Concentration 50 Structure-Activity Relationship In vivo Drug Discovery Humans Structure–activity relationship Potency Enzyme Inhibitors Molecular Biology Cell potency Indole test biology Kinase Chemistry Organic Chemistry Amides In vitro Cell biology Models Chemical Drug Design biology.protein Molecular Medicine
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 22:738-742
ISSN:	0960-894X
Popis:	A series of inhibitors for the 90 kDa ribosomal S6 kinase (RSK) based on an 1-oxo-2,3,4,5-tetrahydro-1H-[1,4]diazepino[1,2-a]indole-8-carboxamide scaffold were optimized for cellular potency and kinase selectivity. This led to the identification of compound 24, BIX 02565, an attractive candidate for use in vitro and in vivo to explore the role of RSK as a target for the treatment heart failure.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0e3a6710f1742d2d831246aeb83ce910 https://doi.org/10.1016/j.bmcl.2011.10.029 Zobrazit plný text záznamu Full Text from ScienceDirect