Title of article
Synthesis and evaluation of substituted benzoisoquinolinones as potent inhibitors of Chk1 kinase
Author/Authors
Robert M. Garbaccio، نويسنده , , Shaei Huang، نويسنده , , Edward S. Tasber، نويسنده , , Mark E. Fraley، نويسنده , , Youwei Yan، نويسنده , , Sanjeev Munshi، نويسنده , , Mari Ikuta، نويسنده , , Lawrence Kuo، نويسنده , , Constanine Kreatsoulas، نويسنده , , Steve Stirdivant، نويسنده , , Bob Drakas، نويسنده , , Keith Rickert، نويسنده , , Eileen S. Walsh، نويسنده , , Kelly A. Hamilton، نويسنده , , Carolyn A. Buser، نويسنده , , James Hardwick، نويسنده , , Xianzhi Mao، نويسنده , , Stephen C. Beck، نويسنده , , Marc T. Abrams، نويسنده , , Weikang Tao، نويسنده , , et al.، نويسنده ,
Issue Information
روزنامه با شماره پیاپی سال 2007
Pages
6
From page
6280
To page
6285
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.
Keywords
Mitotic arrest , p53-Deficient cancer , Checkpoint escape , Apoptosis , Chk1 kinase , Chek1 kinase , cancer , Kinases , Photochemistry , Benzoisoquinolinones , DNA damaging agents , PSA
Journal title
Bioorganic & Medicinal Chemistry Letters
Serial Year
2007
Journal title
Bioorganic & Medicinal Chemistry Letters
Record number
798791
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