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.
GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709-3398, USA. Alex.G.Waterson@gsk.com
Alex G
AG
Waterson
Kirk L
KL
Stevens
Michael J
MJ
Reno
Yue-Mei
YM
Zhang
Eric E
EE
Boros
Frederic
F
Bouvier
Abdullah
A
Rastagar
David E
DE
Uehling
Scott H
SH
Dickerson
Bryan
B
Reep
Octerloney B
OB
McDonald
Edgar R
ER
Wood
David W
DW
Rusnak
Krystal J
KJ
Alligood
Sharon K
SK
Rudolph
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