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

• Published in: Bioorganic & medicinal chemistry Vol. 18; no. 3; pp. 959 - 962
• Main Authors: DUCRAY, Richard, BALLARD, Peter, BARLAAM, Bernard C, HICKINSON, Mark D, KETTLE, Jason G, OGILVIE, Donald J, TRIGWELL, Catherine B
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 01.02.2008
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; Combinatorial Chemistry Techniques; Dogs; Drug Design; General aspects; Medical sciences; Molecular Structure; Pharmacology. Drug treatments; 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; erbB2; Rat; erbB2 Gene; Receptor tyrosine kinase; Epidermal growth factor receptor; Pyridine derivatives; Signal transduction; Pyrazolopyrimidine derivatives; Structure activity relation; Chlorine Organic compounds; Chemical synthesis; Dog; Fissipedia; Carnivora; Enzyme; Transferases; Rodentia; Oral administration; Enzyme inhibitor; Bioavailability; In vitro; Pyrazolopyrimidines; Vertebrata; Growth factor receptor; Mammalia; Animal; Piperazine derivatives; Onc gene; Pharmacokinetics
• ISSN: 0960-894X; 0968-0896; 1464-3405; 1464-3391
• DOI: 10.1016/j.bmcl.2007.12.035

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.