Inhibitors of epidermal growth factor receptor tyrosine kinase: Novel C-5 substituted anilinoquinazolines designed to target the ribose pocket.
A series of novel C-5 substituted anilinoquinazolines, selected on the basis of docking experiments and overlays with ATP in the active site of EGFR tyrosine kinase, have been prepared and found to be potent inhibitors. In vivo pharmacokinetics and disease model activity are discussed.
Ballard
Peter
P
AstraZeneca, Mereside, Alderley Park, Macclesfield, Cheshire SK10 4TG, UK.
Bradbury
Robert H
RH
Harris
Craig S
CS
Hennequin
Laurent F A
LF
Hickinson
Mark
M
Johnson
Paul D
PD
Kettle
Jason G
JG
Klinowska
Teresa
T
Leach
Andrew G
AG
Morgentin
Remy
R
Pass
Martin
M
Ogilvie
Donald J
DJ
Olivier
Annie
A
Warin
Nicolas
N
Williams
Emma J
EJ
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D001665:Binding Sites; D049109:Cell Proliferation / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D005260:Female; D006801:Humans; D007624:KB Cells / Q000187:drug effects; D051379:Mice; D008819:Mice, Nude; D015394:Molecular Structure; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D011799:Quinazolines / Q000138:chemical synthesis / Q000493:pharmacokinetics / Q000494:pharmacology; D051381:Rats; D012266:Ribose / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D012266:Ribose; D000255:Adenosine Triphosphate; D066246:ErbB Receptors