Design and synthesis of potent RSK inhibitors

Autor:	Stephen Basham, Brent A. Appleton, Rama Jain, Lina Setti, Savithri Ramurthy, Paul Feucht, Jiong Lan, Anne B. Jefferson, Laura Doyle, Bob Warne, Mika Lindvall, Sharadha Subramanian, Gordana Atallah, Michelle Mathur, Abran Costales, Cynthia M. Shafer
Rok vydání:	2018
Předmět:	0301 basic medicine Stereochemistry Proton Magnetic Resonance Spectroscopy Clinical Biochemistry Pharmaceutical Science Context (language use) Ring (chemistry) Biochemistry Mass Spectrometry 03 medical and health sciences chemistry.chemical_compound Structure-Activity Relationship Phenols In vivo Drug Discovery Pyridine Moiety Molecule Animals Humans Molecular Biology Protein Kinase Inhibitors Hydrogen bond Organic Chemistry In vitro 030104 developmental biology chemistry Drug Design Molecular Medicine Chromatography Liquid
Zdroj:	Bioorganicmedicinal chemistry letters. 28(19)
ISSN:	1464-3405
Popis:	Utilizing the already described 3,4-bi-aryl pyridine series as a starting point, incorporation of a second ring system with a hydrogen bond donor and additional hydrophobic contacts yielded the azaindole series which exhibited potent, picomolar RSK2 inhibition and the most potent in vitro target modulation seen thus far for a RSK inhibitor. In the context of the more potent core, several changes at the phenol moiety were assessed to potentially find a tool molecule appropriate for in vivo evaluation.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d2f1f7be087371238d9479060ac06a29 https://pubmed.ncbi.nlm.nih.gov/30170943 Zobrazit plný text záznamu Full Text from ScienceDirect