- Optimization of a pyrazoloquinolinone class of Chk1 kinase inhibitors.
Optimization of a pyrazoloquinolinone class of Chk1 kinase inhibitors.
Bioorganic & medicinal chemistry letters (2007-09-07)
Edward J Brnardic, Robert M Garbaccio, Mark E Fraley, Edward S Tasber, Justin T Steen, Kenneth L Arrington, Vadim Y Dudkin, George D Hartman, Steven M Stirdivant, Bob A Drakas, Keith Rickert, Eileen S Walsh, Kelly Hamilton, Carolyn A Buser, James Hardwick, Weikang Tao, Stephen C Beck, Xianzhi Mao, Robert B Lobell, Laura Sepp-Lorenzino, Youwei Yan, Mari Ikuta, Sanjeev K Munshi, Lawrence C Kuo, Constantine Kreatsoulas
PMID17804227
ABSTRACT
The development of 2,5-dihydro-4H-pyrazolo[4,3-c]quinolin-4-ones as inhibitors of Chk1 kinase is described. Introduction of a fused ring at the C7/C8 positions of the pyrazoloquinolinone provided an increase in potency while guidance from overlapping inhibitor bound Chk1 X-ray crystal structures contributed to the discovery of a potent and solubilizing propyl amine moiety in compound 52 (Chk1 IC(50)=3.1 nM).
MATERIALS
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Supelco
Discovery® C8 Supelguard Guard Cartridge Kit, 5 μm particle size, L × I.D. 2 cm × 4 mm, contains 2 nuts, 2 ferrules, 5cm tubing, 1 guard cartridge and 1 guard holder