Novel 3-alkoxy-1H-pyrazolo[3,4-d]pyrimidines as EGFR and erbB2 receptor tyrosine kinase inhibitors.
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.
Ducray
Richard
R
AstraZeneca, Centre de Recherches, Z.I. la Pompelle, BP1050, 51689 Reims Cedex 2, France. richard.ducray@astrazeneca.com
Ballard
Peter
P
Barlaam
Bernard C
BC
Hickinson
Mark D
MD
Kettle
Jason G
JG
Ogilvie
Donald J
DJ
Trigwell
Catherine B
CB
D000818:Animals; D020650:Combinatorial Chemistry Techniques; D004285:Dogs; D015195:Drug Design; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000037:antagonists & inhibitors*; D011720:Pyrazoles / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011743:Pyrimidines / Q000008:administration & dosage / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D020794:Receptor Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*
D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; D020794:Receptor Protein-Tyrosine Kinases; D018719:Erb-b2 Receptor Tyrosine Kinases