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

…, PA Ciecko, KE Coll, C Fernandes, GD Hartman…

Index: Fraley, Mark E.; Arrington, Kenneth L.; Buser, Carolyn A.; Ciecko, Patrice A.; Coll, Kathleen E.; Fernandes, Christine; Hartman, George D.; Hoffman, William F.; Lynch, Joseph J.; McFall, Rosemary C.; Rickert, Keith; Singh, Romi; Smith, Sheri; Thomas, Kenneth A.; Wong, Bradley K. Bioorganic and Medicinal Chemistry Letters, 2004 , vol. 14, # 2 p. 351 - 355

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Citation Number: 53

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 IKr potassium channel hERG.© 2003 Elsevier Science Ltd. All rights reserved.