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 11 was synthesized and found to have potent dual EGFR/HER2 kinase inhibitory activity. The design, synthesis, and proposed binding conformation of 11 in EGFR kinase is described. A novel 5-[1,3,4-oxadiazol-2-yl]-N-aryl-4,6-pyrimidine dia...

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Veröffentlicht in:	Bioorganic & medicinal chemistry 2008-09, Vol.18 (17), p.4896-4899
Hauptverfasser:	Hughes, Terry V., Xu, Guozhang, Wetter, Steven K., Connolly, Peter J., Emanuel, Stuart L., Karnachi, Prabha, Pollack, Scott R., Pandey, Niranjan, Adams, Mary, Moreno-Mazza, Sandra, Middleton, Steven A., Greenberger, Lee M.
Format:	Artikel
Sprache:	eng
Schlagworte:	Antineoplastic agents Biological and medical sciences Bones, joints and connective tissue. Antiinflammatory agents Cell Line Diamines - chemical synthesis Diamines - metabolism Diamines - pharmacology Drug Design EGFR General aspects HeLa Cells HER1 HER2 Humans Intramolecular hydrogen bond Kinase Medical sciences Oxadiazole Oxadiazoles - chemical synthesis Oxadiazoles - metabolism Oxadiazoles - pharmacology Pharmacology. Drug treatments Protein Binding Pyrimidine Pyrimidines - chemical synthesis Pyrimidines - metabolism Pyrimidines - pharmacology Quinazoline mimic Receptor, Epidermal Growth Factor - antagonists & inhibitors Receptor, Epidermal Growth Factor - metabolism Receptor, ErbB-2 - antagonists & inhibitors Receptor, ErbB-2 - metabolism Restricted rotation Structure-Activity Relationship
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Zusammenfassung:	A novel 5-[1,3,4-oxadiazol-2-yl]-N-aryl-4,6-pyrimidine diamine 11 was synthesized and found to have potent dual EGFR/HER2 kinase inhibitory activity. The design, synthesis, and proposed binding conformation of 11 in EGFR kinase is described. 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.
ISSN:	0960-894X 0968-0896 1464-3405 1464-3391
DOI:	10.1016/j.bmcl.2008.07.057