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Neutral 5-substituted 4-indazolylaminoquinazolines as potent, orally active inhibitors of erbB2 receptor tyrosine kinase |
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| Authors: | Barlaam Bernard Acton David G Ballard Peter Bradbury Robert H Cross Darren Ducray Richard Germain Hervé Hudson Kevin Klinowska Teresa Magnien Françoise Ogilvie Donald J Olivier Annie Ross Helen S Smith Robin Trigwell Cath B Vautier Michel Wright Lindsay |
| Affiliation: | AstraZeneca, Centre de Recherches, Z.I.S.E. La Pompelle, B.P. 1050, 51689 Reims Cedex 2, France. bernard.barlaam2@astrazeneca.com |
| Abstract: | We have identified a new series of C-5 substituted indazolylaminoquinazolines as potent erbB2 kinase inhibitors. The lead compound 22 showed excellent in vitro potency, good physical properties, acceptable oral pharmacokinetics in rat and dog, and low human in vitro clearance. It showed at least equivalent activity dose for dose compared to lapatinib in various erbB2- or EGFR-driven xenograft models after chronic oral administration. |
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