Structure-based optimization of potent PDK1 inhibitors

✍ Scribed by Mauro Angiolini; Patrizia Banfi; Elena Casale; Francesco Casuscelli; Claudio Fiorelli; Maria B. Saccardo; Marco Silvagni; Fabio Zuccotto

• Book ID: 104004451
• Publisher: Elsevier Science
• Year: 2010
• Tongue: English
• Weight: 647 KB
• Volume: 20
• Category: Article
• ISSN: 0960-894X
• DOI: 10.1016/j.bmcl.2010.05.070

✦ Synopsis

In this Letter is described the structure-based design of potent dihydro-pyrazoloquinazolines as PDK1 inhibitors. Starting from low potency HTS hits with the aid of X-ray crystallography and modeling, a medicinal chemistry activity was carried out to improve potency versus PDK1 and selectivity versus CDK2 protein kinase.