Novel 3-alkoxy-1H-pyrazolo[3,4-d]pyrimidines as EGFR and erbB2 receptor tyrosine kinase inhibitors

Richard Ducray; Peter Ballard; Bernard C Barlaam; Mark D Hickinson; Jason G Kettle; Donald J Ogilvie; Catherine B Trigwell

doi:10.1016/j.bmcl.2007.12.035

Novel 3-alkoxy-1H-pyrazolo[3,4-d]pyrimidines as EGFR and erbB2 receptor tyrosine kinase inhibitors

Bioorg Med Chem Lett. 2008 Feb 1;18(3):959-62. doi: 10.1016/j.bmcl.2007.12.035. Epub 2007 Dec 23.

Authors

Richard Ducray¹, Peter Ballard, Bernard C Barlaam, Mark D Hickinson, Jason G Kettle, Donald J Ogilvie, Catherine B Trigwell

Affiliation

¹ AstraZeneca, Centre de Recherches, Z.I. la Pompelle, BP1050, 51689 Reims Cedex 2, France. richard.ducray@astrazeneca.com

PMID: 18182285
DOI: 10.1016/j.bmcl.2007.12.035

Abstract

Novel 4-anilino-1H-pyrazolo[3,4-d]pyrimidines have been synthesized and evaluated in vitro for erbB2 and EGFR kinase inhibition. A representative compound displaying oral bioavailability in rat and dog illustrates the potential of this series to provide orally active erbB2 inhibitors.

MeSH terms

Animals
Combinatorial Chemistry Techniques
Dogs
Drug Design
Molecular Structure
Protein Kinase Inhibitors / antagonists & inhibitors*
Pyrazoles / administration & dosage
Pyrazoles / chemical synthesis*
Pyrazoles / chemistry
Pyrazoles / pharmacology*
Pyrimidines / administration & dosage
Pyrimidines / chemical synthesis*
Pyrimidines / chemistry
Pyrimidines / pharmacology*
Rats
Receptor Protein-Tyrosine Kinases / antagonists & inhibitors*
Receptor, ErbB-2 / antagonists & inhibitors*

Substances

Protein Kinase Inhibitors
Pyrazoles
Pyrimidines
Receptor Protein-Tyrosine Kinases
Receptor, ErbB-2