Dual EGFR/ErbB-2 inhibitors from novel pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines

Robert D. Hubbard; Scott H. Dickerson; Holly K. Emerson; Robert J. Griffin; Michael J. Reno; Keith R. Hornberger; David W. Rusnak; Edgar R. Wood; David E. Uehling; Alex G. Waterson

doi:10.1016/j.bmcl.2008.09.090

Dual EGFR/ErbB-2 inhibitors from novel pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines

Robert D. Hubbard, Scott H. Dickerson, Holly K. Emerson, Robert J. Griffin, Michael J. Reno, Keith R. Hornberger, David W. Rusnak, Edgar R. Wood, David E. Uehling, Alex G. Waterson

Cooperative Programs for the Advancement of Earth System Science

GlaxoSmithKline

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

38 Scopus citations

Abstract

A novel class of substituted pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines has been identified that are potent and selective inhibitors of both EGFR/ErbB-2 receptor tyrosine kinases. The inhibitors are found to display a range of enzyme and cellular potency and also to display a varying level of covalent modification of the kinase targets. Selected molecules, including compound 15h, were found to be potent in enzymatic and cellular assays while also demonstrating exposure in the mouse from an oral dose.

Original language	English
Pages (from-to)	5738-5740
Number of pages	3
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	18
Issue number	21
DOIs	https://doi.org/10.1016/j.bmcl.2008.09.090
State	Published - Nov 1 2008

Keywords

EGFR
Epidermal growth factor receptor
ErbB-2
Inhibitor
Thieno[3,2-d]pyrimidines

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10.1016/j.bmcl.2008.09.090

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title = "Dual EGFR/ErbB-2 inhibitors from novel pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines",

abstract = "A novel class of substituted pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines has been identified that are potent and selective inhibitors of both EGFR/ErbB-2 receptor tyrosine kinases. The inhibitors are found to display a range of enzyme and cellular potency and also to display a varying level of covalent modification of the kinase targets. Selected molecules, including compound 15h, were found to be potent in enzymatic and cellular assays while also demonstrating exposure in the mouse from an oral dose.",

keywords = "EGFR, Epidermal growth factor receptor, ErbB-2, Inhibitor, Thieno[3,2-d]pyrimidines",

author = "Hubbard, \{Robert D.\} and Dickerson, \{Scott H.\} and Emerson, \{Holly K.\} and Griffin, \{Robert J.\} and Reno, \{Michael J.\} and Hornberger, \{Keith R.\} and Rusnak, \{David W.\} and Wood, \{Edgar R.\} and Uehling, \{David E.\} and Waterson, \{Alex G.\}",

year = "2008",

month = nov,

day = "1",

doi = "10.1016/j.bmcl.2008.09.090",

language = "English",

volume = "18",

pages = "5738--5740",

journal = "Bioorganic and Medicinal Chemistry Letters",

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TY - JOUR

T1 - Dual EGFR/ErbB-2 inhibitors from novel pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines

AU - Hubbard, Robert D.

AU - Dickerson, Scott H.

AU - Emerson, Holly K.

AU - Griffin, Robert J.

AU - Reno, Michael J.

AU - Hornberger, Keith R.

AU - Rusnak, David W.

AU - Wood, Edgar R.

AU - Uehling, David E.

AU - Waterson, Alex G.

PY - 2008/11/1

Y1 - 2008/11/1

N2 - A novel class of substituted pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines has been identified that are potent and selective inhibitors of both EGFR/ErbB-2 receptor tyrosine kinases. The inhibitors are found to display a range of enzyme and cellular potency and also to display a varying level of covalent modification of the kinase targets. Selected molecules, including compound 15h, were found to be potent in enzymatic and cellular assays while also demonstrating exposure in the mouse from an oral dose.

AB - A novel class of substituted pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines has been identified that are potent and selective inhibitors of both EGFR/ErbB-2 receptor tyrosine kinases. The inhibitors are found to display a range of enzyme and cellular potency and also to display a varying level of covalent modification of the kinase targets. Selected molecules, including compound 15h, were found to be potent in enzymatic and cellular assays while also demonstrating exposure in the mouse from an oral dose.

KW - EGFR

KW - Epidermal growth factor receptor

KW - ErbB-2

KW - Inhibitor

KW - Thieno[3,2-d]pyrimidines

UR - https://www.scopus.com/pages/publications/53949105451

U2 - 10.1016/j.bmcl.2008.09.090

DO - 10.1016/j.bmcl.2008.09.090

M3 - Article

C2 - 18842405

AN - SCOPUS:53949105451

SN - 0960-894X

VL - 18

SP - 5738

EP - 5740

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 21

ER -

Dual EGFR/ErbB-2 inhibitors from novel pyrrolidinyl-acetylenic thieno[3,2-d]pyrimidines

Abstract

Keywords

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