Indolinone based phosphoinositide-dependent kinase-1 (PDK1) inhibitors. Part 2: optimization of BX-517

Autor:	Arnaiz Damian O, Judi Bryant, Richard I. Feldman, Mark A. Polokoff, Gary Phillips, Paul Hrvatin, Marc Adler, James M. Wu, Babu Subramanyam, Dao Lentz, Imadul Islam, Marc Whitlow, Daguang Zhu, Kochanny Monica, Jun Shen, Janette Walters, Shendong Yuan, Elena Ho, Greg Brown
Rok vydání:	2007
Předmět:	Indoles Molecular model Stereochemistry medicine.drug_class Clinical Biochemistry Pharmaceutical Science Carboxamide Protein Serine-Threonine Kinases Biochemistry Chemical synthesis 3-Phosphoinositide-Dependent Protein Kinases chemistry.chemical_compound Cell Line Tumor Drug Discovery medicine Humans Urea Molecular Biology Protein Kinase Inhibitors ADME Pyrrole Bicyclic molecule Organic Chemistry chemistry Lactam Molecular Medicine Lead compound
Zdroj:	Bioorganicmedicinal chemistry letters. 17(14)
ISSN:	0960-894X
Popis:	Based on the lead compound BX-517, a series of C-4' substituted indolinones have been synthesized and evaluated for PDK1 inhibition. Modification at C-4' of the pyrrole afforded potent compounds (7b and 7d) with improved solubility and ADME properties. In this letter, we describe the synthesis, selectivity profile, and pharmacokinetic data of selected compounds.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::69ccd70016040387d3840477d0ee0a34 https://pubmed.ncbi.nlm.nih.gov/17544272 Zobrazit plný text záznamu Full Text from ScienceDirect