The design, synthesis, and biological evaluation of PIM kinase inhibitors

Autor:	John M. Nuss, Gordon Mark Stott, Hongwang Du, E.S. Koltun, A.D Laird, I Ngan, Amy Lew Tsuhako, Adam A. Galan, Ping Huang, Thomas J. Stout, Patrick Kearney, Chan, Stuart Johnston, W. Zhang, R Lin, Stefan Engst, Peiwen Zhou, L Mock, Maurizio Franzini, Brown S David, Moon Hwan Kim, Brian Kane, Naing Aay, Arlyn Arcalas, Wei Xu, Michael Pack, Peiwen Yu, Cristiana A. Zaharia
Rok vydání:	2012
Předmět:	Clinical Biochemistry Pharmaceutical Science Pyrimidinones Crystallography X-Ray Biochemistry Structure-Activity Relationship chemistry.chemical_compound Proto-Oncogene Proteins c-pim-1 hemic and lymphatic diseases Drug Discovery Transferase Computer Simulation Furans Protein Kinase Inhibitors Molecular Biology Cell permeability Alkyl Biological evaluation chemistry.chemical_classification Binding Sites Kinase Aryl Organic Chemistry Combinatorial chemistry Protein Structure Tertiary chemistry Design synthesis Drug Design Molecular Medicine Selectivity
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 22:3732-3738
ISSN:	0960-894X
DOI:	10.1016/j.bmcl.2012.04.025
Popis:	A series of substituted benzofuropyrimidinones with pan-PIM activities and excellent selectivity against a panel of diverse kinases is described. Initial exploration identified aryl benzofuropyrimidinones that were potent, but had cell permeability limitation. Using X-ray crystal structures of the bound PIM-1 complexes with 3, 5m, and 6d, we were able to guide the SAR and identify the alkyl benzofuropyrimidinone (6l) with good PIM potencies, permeability, and oral exposure.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::84ad4fc4a63c7985616e1d826de93fb2 https://doi.org/10.1016/j.bmcl.2012.04.025 Zobrazit plný text záznamu Full Text from ScienceDirect