2-Anilino-4-aryl-8H-purine derivatives as inhibitors of PDK1

Autor:	Chang Kai Soh, Kay Lin Goh, Meredith Williams, Kantharaj Ethirajulu, Haishan Wang, Zahid Bonday, Jeanette Marjorie Wood, Miah Kiat Goh, Kee Chuan Goh, Brian Dymock, Anders Poulsen, Stéphanie Blanchard, Mohammed Khalid Pasha, Chai Ping Lee
Rok vydání:	2012
Předmět:	Clinical Biochemistry Pharmaceutical Science Protein Serine-Threonine Kinases Pharmacology Biochemistry Small Molecule Libraries Inhibitory Concentration 50 Mice Cell Line Tumor Drug Discovery Animals Humans Enzyme Inhibitors Molecular Biology Protein kinase B Cells Cultured PI3K/AKT/mTOR pathway ADME Aniline Compounds Molecular Structure biology Kinase Cell growth Akt/PKB signaling pathway Chemistry Organic Chemistry Cyclin-dependent kinase 2 Pyruvate Dehydrogenase Acetyl-Transferring Kinase Enzyme Activation Solubility Purines Cancer cell biology.protein Molecular Medicine
Zdroj:	Bioorganic & Medicinal Chemistry Letters. 22:2880-2884
ISSN:	0960-894X
Popis:	A series of 2-anilino substituted 4-aryl-8H-purines were prepared as potent inhibitors of PDK1, a serine-threonine kinase thought to play a role in the PI3K/Akt signaling pathway, a key mediator of cancer cell growth, survival and tumorigenesis. The synthesis, SAR and ADME properties of this series of compounds are discussed culminating in the discovery of compound 6 which possessed sub-micromolar cell proliferation activity and 65% oral bioavailability in mice.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::51e326a1e8754536639d26a7d08fc874 https://doi.org/10.1016/j.bmcl.2012.02.058 Zobrazit plný text záznamu Full Text from ScienceDirect