Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1373242 | Bioorganic & Medicinal Chemistry Letters | 2007 | 6 Pages |
Abstract
From HTS lead 1, a novel benzoisoquinolinone class of ATP-competitive Chk1 inhibitors was devised and synthesized via a photochemical route. Using X-ray crystallography as a guide, potency was rapidly enhanced through the installation of a tethered basic amine designed to interact with an acidic residue (Glu91) in the enzyme pocket. Further SAR was explored at the solvent front and near to the H1 pocket and resulted in the discovery of low MW, sub-nanomolar inhibitors of Chk1.
Graphical abstractBenzoisoquinolinones (i.e., 55) are reported as potent inhibitors of Chk1 kinase.Figure optionsDownload full-size imageDownload as PowerPoint slide
Related Topics
Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Robert M. Garbaccio, Shaei Huang, Edward S. Tasber, Mark E. Fraley, Youwei Yan, Sanjeev Munshi, Mari Ikuta, Lawrence Kuo, Constanine Kreatsoulas, Steve Stirdivant, Bob Drakas, Keith Rickert, Eileen S. Walsh, Kelly A. Hamilton, Carolyn A. Buser,