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

Terry V Hughes; Guozhang Xu; Steven K Wetter; Peter J Connolly; Stuart L Emanuel; Prabha Karnachi; Scott R Pollack; Niranjan Pandey; Mary Adams; Sandra Moreno-Mazza; Steven A Middleton; Lee M Greenberger

doi:10.1016/j.bmcl.2008.07.057

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

Bioorg Med Chem Lett. 2008 Sep 1;18(17):4896-9. doi: 10.1016/j.bmcl.2008.07.057. Epub 2008 Jul 17.

Authors

Terry V Hughes¹, Guozhang Xu, Steven K Wetter, Peter J Connolly, Stuart L Emanuel, Prabha Karnachi, Scott R Pollack, Niranjan Pandey, Mary Adams, Sandra Moreno-Mazza, Steven A Middleton, Lee M Greenberger

Affiliation

¹ Johnson & Johnson Pharmaceutical Research and Development, L.L.C., PO Box 300, 1000 Route 202, Raritan, NJ 08869, USA.

PMID: 18678484
DOI: 10.1016/j.bmcl.2008.07.057

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.

Publication types

Comparative Study

MeSH terms

Cell Line
Diamines / chemical synthesis
Diamines / metabolism
Diamines / pharmacology*
Drug Design
ErbB Receptors / antagonists & inhibitors
ErbB Receptors / metabolism*
HeLa Cells
Humans
Oxadiazoles / chemical synthesis
Oxadiazoles / metabolism
Oxadiazoles / pharmacology*
Protein Binding
Pyrimidines / chemical synthesis
Pyrimidines / metabolism
Pyrimidines / pharmacology*
Receptor, ErbB-2 / antagonists & inhibitors
Receptor, ErbB-2 / metabolism*
Structure-Activity Relationship

Substances

Diamines
Oxadiazoles
Pyrimidines
ErbB Receptors
Receptor, ErbB-2