Discovery of potent and selective Spleen Tyrosine Kinase inhibitors for the topical treatment of inflammatory skin disease

Autor:	Michael David Barker, Emma J. Jones, Robert J. Watson, Huw D. Lewis, Cesar Ramirez-Molina, David Matthew Wilson, Marion C. Dickson, Robert P. Davis, Francis Louis Atkinson, Margarete Neu, Donald O. Somers, John Liddle
Rok vydání:	2018
Předmět:	0301 basic medicine Pyridines Administration Topical Clinical Biochemistry Anti-Inflammatory Agents Pharmaceutical Science Syk Topical treatment Human skin Biochemistry Structure-Activity Relationship 03 medical and health sciences 0302 clinical medicine Catalytic Domain Cell Line Tumor Drug Discovery Humans Syk Kinase Potency Transferase Protein Kinase Inhibitors Molecular Biology Skin Molecular Structure Chemistry Inflammatory skin disease Organic Chemistry Molecular Docking Simulation enzymes and coenzymes (carbohydrates) 030104 developmental biology 030220 oncology & carcinogenesis Skin penetration Cancer research Molecular Medicine biological phenomena cell phenomena and immunity
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 28:3458-3462
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2018.09.022
Popis:	The discovery and lead optimisation of a novel series of SYK inhibitors is described. These were optimised for SYK potency and selectivity against Aurora B. Compounds were profiled in a human skin penetration study to identify a suitable candidate molecule for pre-clinical development. Compound 44 (GSK2646264) was selected for progression and is currently in Phase I clinical trials.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ea0edda7c25304f4d66d8a85ae30e56a https://doi.org/10.1016/j.bmcl.2018.09.022 Zobrazit plný text záznamu Full Text from ScienceDirect