Thienopyridine urea inhibitors of KDR kinase

H. Robin Heyman; Robin R. Frey; Peter F. Bousquet; George A. Cunha; Maria D. Moskey; Asma A. Ahmed; Niru B. Soni; Patrick A. Marcotte; Lori J. Pease; Keith B. Glaser; Melinda Yates; Jennifer J. Bouska; Daniel H. Albert; Candace L. Black-Schaefer; Peter J. Dandliker; Kent D. Stewart; Paul Rafferty; Steven K. Davidsen; Michael R. Michaelides; Michael L. Curtin

doi:10.1016/j.bmcl.2006.12.015

Thienopyridine urea inhibitors of KDR kinase

H. Robin Heyman
, Robin R. Frey
, Peter F. Bousquet
, George A. Cunha
, Maria D. Moskey
, Asma A. Ahmed
, Niru B. Soni
, Patrick A. Marcotte
, Lori J. Pease
, Keith B. Glaser
, Melinda Yates
, Jennifer J. Bouska
, Daniel H. Albert
, Candace L. Black-Schaefer
, Peter J. Dandliker
, Kent D. Stewart
, Paul Rafferty
, Steven K. Davidsen
, Michael R. Michaelides
, Michael L. Curtin

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

43 Scopus citations

Abstract

A series of substituted thienopyridine ureas was prepared and evaluated for enzymatic and cellular inhibition of KDR kinase activity. Several of these analogs, such as 2, are potent inhibitors of KDR (<10 nM) in both enzymatic and cellular assays. Further characterization of inhibitor 2 indicated that this analog possessed excellent in vivo potency (ED₅₀ 2.1 mg/kg) as measured in an estradiol-induced mouse uterine edema model.

Original language	English (US)
Pages (from-to)	1246-1249
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	17
Issue number	5
DOIs	https://doi.org/10.1016/j.bmcl.2006.12.015
State	Published - Mar 1 2007
Externally published	Yes

Keywords

KDR kinase
Thienopyridine
Urea
VEGF

ASJC Scopus subject areas

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

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10.1016/j.bmcl.2006.12.015

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Heyman, H. R., Frey, R. R., Bousquet, P. F., Cunha, G. A., Moskey, M. D., Ahmed, A. A., Soni, N. B., Marcotte, P. A., Pease, L. J., Glaser, K. B., Yates, M., Bouska, J. J., Albert, D. H., Black-Schaefer, C. L., Dandliker, P. J., Stewart, K. D., Rafferty, P., Davidsen, S. K., Michaelides, M. R., & Curtin, M. L. (2007). Thienopyridine urea inhibitors of KDR kinase. Bioorganic and Medicinal Chemistry Letters, 17(5), 1246-1249. https://doi.org/10.1016/j.bmcl.2006.12.015

Heyman, HR, Frey, RR, Bousquet, PF, Cunha, GA, Moskey, MD, Ahmed, AA, Soni, NB, Marcotte, PA, Pease, LJ, Glaser, KB, Yates, M, Bouska, JJ, Albert, DH, Black-Schaefer, CL, Dandliker, PJ, Stewart, KD, Rafferty, P, Davidsen, SK, Michaelides, MR & Curtin, ML 2007, 'Thienopyridine urea inhibitors of KDR kinase', Bioorganic and Medicinal Chemistry Letters, vol. 17, no. 5, pp. 1246-1249. https://doi.org/10.1016/j.bmcl.2006.12.015

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title = "Thienopyridine urea inhibitors of KDR kinase",

abstract = "A series of substituted thienopyridine ureas was prepared and evaluated for enzymatic and cellular inhibition of KDR kinase activity. Several of these analogs, such as 2, are potent inhibitors of KDR (<10 nM) in both enzymatic and cellular assays. Further characterization of inhibitor 2 indicated that this analog possessed excellent in vivo potency (ED50 2.1 mg/kg) as measured in an estradiol-induced mouse uterine edema model.",

keywords = "KDR kinase, Thienopyridine, Urea, VEGF",

author = "Heyman, \{H. Robin\} and Frey, \{Robin R.\} and Bousquet, \{Peter F.\} and Cunha, \{George A.\} and Moskey, \{Maria D.\} and Ahmed, \{Asma A.\} and Soni, \{Niru B.\} and Marcotte, \{Patrick A.\} and Pease, \{Lori J.\} and Glaser, \{Keith B.\} and Melinda Yates and Bouska, \{Jennifer J.\} and Albert, \{Daniel H.\} and Black-Schaefer, \{Candace L.\} and Dandliker, \{Peter J.\} and Stewart, \{Kent D.\} and Paul Rafferty and Davidsen, \{Steven K.\} and Michaelides, \{Michael R.\} and Curtin, \{Michael L.\}",

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doi = "10.1016/j.bmcl.2006.12.015",

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AU - Heyman, H. Robin

AU - Frey, Robin R.

AU - Bousquet, Peter F.

AU - Cunha, George A.

AU - Moskey, Maria D.

AU - Ahmed, Asma A.

AU - Soni, Niru B.

AU - Marcotte, Patrick A.

AU - Pease, Lori J.

AU - Glaser, Keith B.

AU - Yates, Melinda

AU - Bouska, Jennifer J.

AU - Albert, Daniel H.

AU - Black-Schaefer, Candace L.

AU - Dandliker, Peter J.

AU - Stewart, Kent D.

AU - Rafferty, Paul

AU - Davidsen, Steven K.

AU - Michaelides, Michael R.

AU - Curtin, Michael L.

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AB - A series of substituted thienopyridine ureas was prepared and evaluated for enzymatic and cellular inhibition of KDR kinase activity. Several of these analogs, such as 2, are potent inhibitors of KDR (<10 nM) in both enzymatic and cellular assays. Further characterization of inhibitor 2 indicated that this analog possessed excellent in vivo potency (ED50 2.1 mg/kg) as measured in an estradiol-induced mouse uterine edema model.

KW - KDR kinase

KW - Thienopyridine

KW - Urea

KW - VEGF

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UR - https://www.scopus.com/pages/publications/33846902851#tab=citedBy

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M3 - Article

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AN - SCOPUS:33846902851

SN - 0960-894X

VL - 17

SP - 1246

EP - 1249

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 5

ER -

Thienopyridine urea inhibitors of KDR kinase

Abstract

Keywords

ASJC Scopus subject areas

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