Discovery and optimization of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1

Autor:	Darlene Romashko, James G. Tarrant, Felix Weng, Keith R. Hornberger, Matthew R. Medeiros, Andrew Kleinberg, Peter Meyn, Dan Maarten Berger, Mark Albertella, William Peick, An-Hu Li, Mark Bittner, Jing Wang, Hanqing Dong, Paul Maresca, Mark J. Mulvihill, Earl W. May, Wilde Victoria Lynn, Kam W. Siu, Brianna Tokar, Michael Tanowitz, Michael J. Gray, Andrew P. Crew, Andrew Cooke
Rok vydání:	2013
Předmět:	Stereochemistry Pyridines Clinical Biochemistry Pharmaceutical Science Crystallography X-Ray Biochemistry chemistry.chemical_compound Inhibitory Concentration 50 Mice Structure-Activity Relationship Neoplasms Drug Discovery Pyridine Potency Animals Humans Amines Enzyme Inhibitors Furans Molecular Biology Molecular Structure Chemistry Organic Chemistry MAP Kinase Kinase Kinases Xenograft Model Antitumor Assays Enzyme Activation Drug Design Molecular Medicine
Zdroj:	Bioorganicmedicinal chemistry letters. 23(16)
ISSN:	1464-3405
Popis:	The discovery and potency optimization of a series of 7-aminofuro[2,3-c]pyridine inhibitors of TAK1 is described. Micromolar hits taken from high-throughput screening were optimized for biochemical and cellular mechanistic potency to ∼10 nM, as exemplified by compound 12az. Application of structure-based drug design aided by co-crystal structures of TAK1 with inhibitors significantly shortened the number of iterations required for the optimization.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::539f984e43b2488a1efbebe0b4c06384 https://pubmed.ncbi.nlm.nih.gov/23850198 Zobrazit plný text záznamu Full Text from ScienceDirect