Alkynyl pyrimidines as dual EGFR/ErbB2 kinase inhibitors.
Anilinoalkynylpyrimidines were prepared and evaluated as dual EGFR/ErbB2 kinase inhibitors. A preference was found for substituted phenyl and heteroaromatic rings attached to the alkyne. In addition, the presence of a potential hydrogen bond donor appended to this ring was favored. Selected molecules in the series demonstrated some activity against human tumor cell lines.
Waterson
Alex G
AG
GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA. Alex.G.Waterson@gsk.com
Stevens
Kirk L
KL
Reno
Michael J
MJ
Zhang
Yue-Mei
YM
Boros
Eric E
EE
Bouvier
Frederic
F
Rastagar
Abdullah
A
Uehling
David E
DE
Dickerson
Scott H
SH
Reep
Bryan
B
McDonald
Octerloney B
OB
Wood
Edgar R
ER
Rusnak
David W
DW
Alligood
Krystal J
KJ
Rudolph
Sharon K
SK
D000480:Alkynes / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D000480:Alkynes; D066246:ErbB Receptors; D011743:Pyrimidines; D018719:Erb-b2 Receptor Tyrosine Kinases