A novel 5-[1,3,4-oxadiazol-2-yl]-N-aryl-4,6-pyrimidine diamine having dual EGFR/HER2 kinase activity: design, synthesis, and biological activity.
A novel 5-[1,3,4-oxadiazol-2-yl]-N-aryl-4,6-pyrimidine diamine was synthesized and found to have potent dual EGFR/HER2 kinase inhibitory activity. The structure-based drug design of this molecule as well as the kinase and cellular inhibition of HER2 kinase dependent cell lines will be discussed.
Hughes
Terry V
TV
Johnson & Johnson Pharmaceutical Research and Development, L.L.C., PO Box 300, 1000 Route 202, Raritan, NJ 08869, USA.
Xu
Guozhang
G
Wetter
Steven K
SK
Connolly
Peter J
PJ
Emanuel
Stuart L
SL
Karnachi
Prabha
P
Pollack
Scott R
SR
Pandey
Niranjan
N
Adams
Mary
M
Moreno-Mazza
Sandra
S
Middleton
Steven A
SA
Greenberger
Lee M
LM
D002460:Cell Line; D003959:Diamines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D015195:Drug Design; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D011485:Protein Binding; D011743:Pyrimidines / Q000138:chemical synthesis / Q000378:metabolism / Q000494:pharmacology*; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013329:Structure-Activity Relationship
D003959:Diamines; D066246:ErbB Receptors; D010069:Oxadiazoles; D011743:Pyrimidines; D018719:Erb-b2 Receptor Tyrosine Kinases