Optimization of the indolyl quinolinone class of KDR (VEGFR-2) kinase inhibitors: effects of 5-amido- and 5-sulphonamido-indolyl groups on pharmacokinetics and hERG binding

Mark E Fraley,Kenneth L Arrington,Carolyn A Buser,Patrice A Ciecko,Kathleen E Coll,Christine Fernandes,George D Hartman,William F Hoffman,Joseph J Lynch,Rosemary C Mcfall,Keith Rickert,Romi Singh,Sheri Smith,Kenneth A Thomas,Bradley K Wong

doi:10.1016/j.bmcl.2003.11.007

Optimization of the indolyl quinolinone class of KDR (VEGFR-2) kinase inhibitors: effects of 5-amido- and 5-sulphonamido-indolyl groups on pharmacokinetics and hERG binding

Mark E Fraley, Kenneth L Arrington + Show 13 more

https://doi.org/10.1016/j.bmcl.2003.11.007

Copy DOI

Journal: Bioorganic & Medicinal Chemistry Letters	Publication Date: Dec 6, 2003
Citations: 60

Affiliation: United States Military Academy

#KDR Kinase Inhibitors #KDR Kinase + Show 8 more

Abstract
Full-Text PDF
Similar Papers

Abstract

Modifications to the basic side-chain of early lead structures of the indolyl quinolinone class of KDR kinase inhibitors resulted in improved pharmacokinetic and ancillary profiles. Specifically, compounds bearing 5-amido- and 5-sulphonamido-indolyl substituents exhibited lower plasma clearance and weaker binding affinity for the I Kr potassium channel hERG. ©2003 Elsevier Science Ltd. All rights reserved.

Full Text