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

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

Research output: Contribution to journal › Article › peer-review

22 Scopus citations

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.

Original language	English (US)
Pages (from-to)	4896-4899
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	17
DOIs	https://doi.org/10.1016/j.bmcl.2008.07.057
State	Published - Sep 1 2008
Externally published	Yes

Keywords

EGFR
HER1
HER2
Intramolecular hydrogen bond
Kinase
Oxadiazole
Pyrimidine
Quinazoline mimic
Restricted rotation

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

Access to Document

10.1016/j.bmcl.2008.07.057

Cite this

Hughes, T. V., Xu, G., Wetter, S. K., Connolly, P. J., Emanuel, S. L., Karnachi, P., Pollack, S. R., Pandey, N., Adams, M., Moreno-Mazza, S., Middleton, S. A., & Greenberger, L. M. (2008). 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. Bioorganic and Medicinal Chemistry Letters, 18(17), 4896-4899. https://doi.org/10.1016/j.bmcl.2008.07.057

Hughes, TV, Xu, G, Wetter, SK, Connolly, PJ, Emanuel, SL, Karnachi, P, Pollack, SR, Pandey, N, Adams, M, Moreno-Mazza, S, Middleton, SA & Greenberger, LM 2008, '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', Bioorganic and Medicinal Chemistry Letters, vol. 18, no. 17, pp. 4896-4899. https://doi.org/10.1016/j.bmcl.2008.07.057

@article{376c0247abc847919ba558aa430a8330,

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.",

keywords = "EGFR, HER1, HER2, Intramolecular hydrogen bond, Kinase, Oxadiazole, Pyrimidine, Quinazoline mimic, Restricted rotation",

author = "Hughes, {Terry V.} and Guozhang Xu and Wetter, {Steven K.} and Connolly, {Peter J.} and Emanuel, {Stuart L.} and Prabha Karnachi and Pollack, {Scott R.} and Niranjan Pandey and Mary Adams and Sandra Moreno-Mazza and Middleton, {Steven A.} and Greenberger, {Lee M.}",

year = "2008",

month = sep,

day = "1",

doi = "10.1016/j.bmcl.2008.07.057",

language = "English (US)",

volume = "18",

pages = "4896--4899",

journal = "Bioorganic and Medicinal Chemistry Letters",

issn = "0960-894X",

publisher = "Elsevier Limited",

number = "17",

}

TY - JOUR

T1 - A novel 5-[1,3,4-oxadiazol-2-yl]-N-aryl-4,6-pyrimidine diamine having dual EGFR/HER2 kinase activity

T2 - Design, synthesis, and biological activity

AU - Hughes, Terry V.

AU - Xu, Guozhang

AU - Wetter, Steven K.

AU - Connolly, Peter J.

AU - Emanuel, Stuart L.

AU - Karnachi, Prabha

AU - Pollack, Scott R.

AU - Pandey, Niranjan

AU - Adams, Mary

AU - Moreno-Mazza, Sandra

AU - Middleton, Steven A.

AU - Greenberger, Lee M.

PY - 2008/9/1

Y1 - 2008/9/1

N2 - 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.

AB - 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.

KW - EGFR

KW - HER1

KW - HER2

KW - Intramolecular hydrogen bond

KW - Kinase

KW - Oxadiazole

KW - Pyrimidine

KW - Quinazoline mimic

KW - Restricted rotation

UR - http://www.scopus.com/inward/record.url?scp=49849098785&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=49849098785&partnerID=8YFLogxK

U2 - 10.1016/j.bmcl.2008.07.057

DO - 10.1016/j.bmcl.2008.07.057

M3 - Article

C2 - 18678484

AN - SCOPUS:49849098785

SN - 0960-894X

VL - 18

SP - 4896

EP - 4899

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 17

ER -

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

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this