Structure guided design of a series of selective pyrrolopyrimidinone MARK inhibitors

Autor:	Matthew G. Stanton, Sanjeev Munshi, Ian W. Davies, Kaleen Konrad Childers, Michael Hutton, Lee Warren, Mansuo Hayashi, Anna A. Zabierek, Alan B. Northrup, Alexander A. Szewczak, Hugh Nuthall, Andrew M. Haidle, Ben Munoz, Dapeng Chen, Hua-Poo Su, Yongquan Hou, Jason D. Katz, Andreas Harsch, Michael D. Altman, James P. Jewell
Rok vydání:	2017
Předmět:	Models Molecular 0301 basic medicine Stereochemistry Clinical Biochemistry Pharmaceutical Science Pyrimidinones Computational biology Protein Serine-Threonine Kinases Crystallography X-Ray Biochemistry Cell Line Structure-Activity Relationship 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Alzheimer Disease Drug Discovery Humans Pyrroles Protein Kinase Inhibitors Molecular Biology Dose-Response Relationship Drug Molecular Structure Chemistry Organic Chemistry Isoindoline 030104 developmental biology Drug Design Molecular Medicine 030217 neurology & neurosurgery
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 27:114-120
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2016.08.068
Popis:	The initial structure activity relationships around an isoindoline uHTS hit will be described. Information gleaned from ligand co-crystal structures allowed for rapid refinements in both MARK potency and kinase selectivity. These efforts allowed for the identification of a compound with properties suitable for use as an in vitro tool compound for validation studies on MARK as a viable target for Alzheimer's disease.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::20493003f7f8446544809a814383d0f7 https://doi.org/10.1016/j.bmcl.2016.08.068 Zobrazit plný text záznamu Full Text from ScienceDirect