Rational design of 4,5-disubstituted-5,7-dihydro-pyrrolo[2,3-d]pyrimidin-6-ones as a novel class of inhibitors of epidermal growth factor receptor (EGF-R) and Her2(p185(erbB)) tyrosine kinases.
A novel class of 4,5-disubstituted-5,7-dihydro-pyrrolo[2,3-d]pyrimidin-6-ones has been discovered as potent and selective inhibitors of the EGF-R tyrosine kinase family. These compounds selectively inhibit EGF-R kinase activity at low nanomolar concentration and tyrosine autophosphorylation in cells expressing EGF-R or Her2 (p185(erbB)). Structure-activity relationships (SARs) for this class of compounds are presented.
Sun
Li
L
SUGEN, Inc., 230 East Grand Avenue, South San Francisco, CA 94080, USA.
Cui
Jean
J
Liang
Congxin
C
Zhou
Yong
Y
Nematalla
Asaad
A
Wang
Xueyan
X
Chen
Hui
H
Tang
Cho
C
Wei
James
J
D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D015394:Molecular Structure; D010766:Phosphorylation / Q000187:drug effects; D019000:Phosphotyrosine / Q000378:metabolism; D011744:Pyrimidinones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D019000:Phosphotyrosine; D011744:Pyrimidinones; D018719:Erb-b2 Receptor Tyrosine Kinases