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

Victor J Cee; Alan C Cheng; Karina Romero; Steve Bellon; Christopher Mohr; Douglas A Whittington; Annette Bak; James Bready; Sean Caenepeel; Angela Coxon; Holly L Deak; Jenne Fretland; Yan Gu; Brian L Hodous; Xin Huang; Joseph L Kim; Jasmine Lin; Alexander M Long; Hanh Nguyen; Philip R Olivieri; Vinod F Patel; Ling Wang; Yihong Zhou; Paul Hughes; Stephanie Geuns-Meyer

doi:10.1016/j.bmcl.2008.11.056

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

Journal article

Peer reviewed

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

Victor J Cee, Alan C Cheng, Karina Romero, Steve Bellon, Christopher Mohr, Douglas A Whittington, Annette Bak, James Bready, Sean Caenepeel, Angela Coxon, …

Bioorganic & medicinal chemistry letters, Vol.19(2), pp.424-427

2009

DOI: https://doi.org/10.1016/j.bmcl.2008.11.056

PMID: 19062275

Abstract

Angiogenesis

Benzimidazole

Kinase inhibitor

Tie-2 kinase

The optimization of a nonselective scaffold into 15, a potent inhibitor of Tie-2 kinase with selectivity against VEGFR2 kinase, is reported. 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.

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Title: Pyridyl-pyrimidine benzimidazole derivatives as potent, selective, and orally bioavailable inhibitors of Tie-2 kinase
Creators: Victor J Cee - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA
Alan C Cheng - Amgen
Karina Romero - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA
Steve Bellon - Department of Molecular Structure, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA
Christopher Mohr - Department of Molecular Structure, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA
Douglas A Whittington - Department of Molecular Structure, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA
Annette Bak - Department of Pharmaceutics, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA
James Bready - Department of Oncology Research, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA
Sean Caenepeel - Department of Oncology Research, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA
Angela Coxon - Department of Oncology Research, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA
Holly L Deak - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA
Jenne Fretland - Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA
Yan Gu - Department of Molecular Structure, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA
Brian L Hodous - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA
Xin Huang - Department of Molecular Structure, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA
Joseph L Kim - Department of Molecular Structure, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA
Jasmine Lin - Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA
Alexander M Long - Department of Molecular Structure, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA
Hanh Nguyen - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA
Philip R Olivieri - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA
Vinod F Patel - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA
Ling Wang - Department of Oncology Research, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA
Yihong Zhou - Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA
Paul Hughes - Department of Oncology Research, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA
Stephanie Geuns-Meyer - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Bldg. 1000, Cambridge, MA 02139, USA
Publication Details: Bioorganic & medicinal chemistry letters, Vol.19(2), pp.424-427
Publisher: Elsevier Ltd
Identifiers: 9924085996801921
Academic Unit: Rabb School of Continuing Studies, Division of Graduate Professional Studies
Language: English
Resource Type: Journal article

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

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