Pyridyl-pyrimidine benzimidazole derivatives as potent, selective, and orally bioavailable inhibitors of Tie-2 kinase

被引：55

作者：

Cee, Victor J. ^{[1
]}

Cheng, Alan C. ^{[2
,6
]}

Romero, Karina ^{[1
]}

Bellon, Steve ^{[2
,6
]}

Mohr, Christopher ^{[2
,6
]}

Whittington, Douglas A. ^{[2
,6
]}

Bak, Annette ^{[3
]}

Bready, James ^{[5
]}

Caenepeel, Sean ^{[5
]}

Coxon, Angela ^{[5
]}

Deak, Holly L. ^{[1
]}

Fretland, Jenne ^{[4
,7
]}

Gu, Yan ^{[2
,6
]}

Hodous, Brian L. ^{[1
]}

Huang, Xin ^{[2
,6
]}

Kim, Joseph L. ^{[2
,6
]}

Lin, Jasmine ^{[4
,7
]}

Long, Alexander M. ^{[2
,6
]}

Nguyen, Hanh ^{[1
]}

Olivieri, Philip R. ^{[1
]}

Patel, Vinod F. ^{[1
]}

Wang, Ling ^{[5
]}

Zhou, Yihong ^{[4
,7
]}

Hughes, Paul ^{[5
]}

Geuns-Meyer, Stephanie ^{[1
]}

机构：

[1] Amgen Inc, Dept Med Chem, Cambridge, MA 02139 USA

[2] Amgen Inc, Dept Mol Struct, Cambridge, MA 02139 USA

[3] Amgen Inc, Dept Pharmaceut, Cambridge, MA 02139 USA

[4] Amgen Inc, Dept Pharmacokinet & Drug Metab, Cambridge, MA 02139 USA

[5] Amgen Inc, Dept Oncol Res, Thousand Oaks, CA 91320 USA

[6] Amgen Inc, Dept Mol Struct, Thousand Oaks, CA 91320 USA

[7] Amgen Inc, Dept Pharmacokinet & Drug Metab, Thousand Oaks, CA 91320 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 02期

关键词：

Tie-2; kinase; Angiogenesis; Kinase inhibitor; Benzimidazole; ANGIOGENESIS; RECEPTORS;

D O I：

10.1016/j.bmcl.2008.11.056

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Selective small molecule inhibitors of Tie-2 kinase are important tools for the validation of Tie-2 signaling in pathological angiogenesis. Reported herein is the optimization of a nonselective scaffold into a potent and highly selective inhibitor of Tie-2 kinase. (C) 2008 Elsevier Ltd. All rights reserved.

引用

收藏

页码：424 / 427

页数：4

相关论文

共 19 条

[1] The cellular geography of aurora kinases [J].

Carmena, M ;

Earnshaw, WC .

NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2003, 4 (11) :842-854

[2] Alkynylpyrimidine amide derivatives as potent, selective, and orally active inhibitors of tie-2 kinase [J].

Cee, Victor J. ;

Albrecht, Brian K. ;

Geuns-Meyer, Stephanie ;

Hughes, Paul ;

Bellon, Steve ;

Bready, James ;

Caenepeel, Sean ;

Chaffee, Stuart C. ;

Coxon, Angela ;

Emery, Maurice ;

Fretland, Jenne ;

Gallant, Paul ;

Gu, Yan ;

Hodous, Brian L. ;

Hoffman, Doug ;

Johnson, Rebecca E. ;

Kendall, Richard ;

Kim, Joseph L. ;

Long, Alexander M. ;

McGowan, David ;

Morrison, Michael ;

Olivieri, Philip R. ;

Patel, Vinod F. ;

Polverino, Anthony ;

Powers, David ;

Rose, Paul ;

Wang, Ling ;

Zhao, Huilin .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (04) :627-640

[3] A one-pot method for the synthesis of 2-aminobenzimidazoles and related heterocycles [J].

Cee, Victor J. ;

Downing, Nicholas S. .

TETRAHEDRON LETTERS, 2006, 47 (22) :3747-3750

[4]

*CHEM COMP GROUP, SCWRL 3 0 WAS US IN

[5] Recent kinase and kinase inhibitor X-ray structures: Mechanisms of inhibition and selectivity insights [J].

Cherry, M ;

Williams, DH .

CURRENT MEDICINAL CHEMISTRY, 2004, 11 (06) :663-673

[6] The biology of VEGF and its receptors [J].

Ferrara, N ;

Gerber, HP ;

LeCouter, J .

NATURE MEDICINE, 2003, 9 (06) :669-676

[7] ANGIOGENESIS IN CANCER, VASCULAR, RHEUMATOID AND OTHER DISEASE [J].

FOLKMAN, J .

NATURE MEDICINE, 1995, 1 (01) :27-31

[8] Opinion - Angiogenesis: an organizing principle for drug discovery? [J].

Folkman, Judah .

NATURE REVIEWS DRUG DISCOVERY, 2007, 6 (04) :273-286

[9] Evolution of a highly selective and potent 2-(pyridin-2-yl)-1,3,5-triazine tie-2 kinase inhibitor [J].

Hodous, Brian L. ;

Geuns-Meyer, Stephanie D. ;

Hughes, Paul E. ;

Albrecht, Brian K. ;

Bellon, Steve ;

Bready, James ;

Caenepeel, Sean ;

Cee, Victor J. ;

Chaffee, Stuart C. ;

Coxon, Angela ;

Emery, Maurice ;

Fretland, Jenne ;

Gallant, Paul ;

Gu, Yan ;

Hoffman, Doug ;

Johnson, Rebecca E. ;

Kendall, Richard ;

Kim, Joseph L. ;

Long, Alexander M. ;

Morrison, Michael ;

Olivieri, Philip R. ;

Patel, Vinod F. ;

Polverino, Anthony ;

Rose, Paul ;

Tempest, Paul ;

Wang, Ling ;

Whittington, Douglas A. ;

Zhao, Huilin .

JOURNAL OF MEDICINAL CHEMISTRY, 2007, 50 (04) :611-626

[10] Optimization of triarylimidazoles for Tie2: Influence of conformation on potency [J].

Johnson, Neil W. ;

Semones, Marcus ;

Adams, Jerry L. ;

Hansbury, Michael ;

Winkler, Jim .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2007, 17 (20) :5514-5517