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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 |
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| Authors: | 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 |
| Affiliation: | Department of Medicinal Chemistry, Merck Research Laboratories, West Point, PA 19486, USA. mark_fraley@merck.com |
| 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. |
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