title: 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.
abstract: 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.
authors.affiliation: Johnson & Johnson Pharmaceutical Research and Development, L.L.C., PO Box 300, 1000 Route 202, Raritan, NJ 08869, USA.
authors.forename: Terry V
authors.initials: TV
authors.lastname: Hughes
authors.forename: Guozhang
authors.initials: G
authors.lastname: Xu
authors.forename: Steven K
authors.initials: SK
authors.lastname: Wetter
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Connolly
authors.forename: Stuart L
authors.initials: SL
authors.lastname: Emanuel
authors.forename: Prabha
authors.initials: P
authors.lastname: Karnachi
authors.forename: Scott R
authors.initials: SR
authors.lastname: Pollack
authors.forename: Niranjan
authors.initials: N
authors.lastname: Pandey
authors.forename: Mary
authors.initials: M
authors.lastname: Adams
authors.forename: Sandra
authors.initials: S
authors.lastname: Moreno-Mazza
authors.forename: Steven A
authors.initials: SA
authors.lastname: Middleton
authors.forename: Lee M
authors.initials: LM
authors.lastname: Greenberger
mesh_terms: 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
chemical_list: D003959:Diamines; D066246:ErbB Receptors; D010069:Oxadiazoles; D011743:Pyrimidines; D018719:Erb-b2 Receptor Tyrosine Kinases