Discovery of 4-amino-5,6-biaryl-furo[2,3- d]pyrimidines as inhibitors of Lck: Development of an expedient and divergent synthetic route and preliminary SAR

Erin F DiMauro; John Newcomb; Joseph J Nunes; Jean E Bemis; Christina Boucher; John L Buchanan; William H Buckner; Alan Cheng; Theodore Faust; Faye Hsieh; Xin Huang; Josie H Lee; Teresa L Marshall; Matthew W Martin; David C McGowan; Stephen Schneider; Susan M Turci; Ryan D White; Xiaotian Zhu

doi:10.1016/j.bmcl.2007.01.057

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Discovery of 4-amino-5,6-biaryl-furo[2,3- d]pyrimidines as inhibitors of Lck: Development of an expedient and divergent synthetic route and preliminary SAR

Journal article

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Discovery of 4-amino-5,6-biaryl-furo[2,3- d]pyrimidines as inhibitors of Lck: Development of an expedient and divergent synthetic route and preliminary SAR

Erin F DiMauro, John Newcomb, Joseph J Nunes, Jean E Bemis, Christina Boucher, John L Buchanan, William H Buckner, Alan Cheng, Theodore Faust, Faye Hsieh, …

Bioorganic & medicinal chemistry letters, Vol.17(8), pp.2305-2309

2007

DOI: https://doi.org/10.1016/j.bmcl.2007.01.057

PMID: 17280833

Abstract

Anti-inflammatory

Furopyrimidine

Kinase inhibitors

Lymphocyte specific kinase (Lck)

4-Amino-5,6-biaryl-furo[2,3- d]pyrimidines were identified as potent non-selective inhibitors of Lck. A novel, divergent, and practical synthetic route was developed to access derivatives from bifunctional intermediates. Lead optimization was guided by X-ray crystallographic data, and preliminary SAR led to the identification of compounds with improved cellular potency and selectivity.

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Title: Discovery of 4-amino-5,6-biaryl-furo[2,3- d]pyrimidines as inhibitors of Lck: Development of an expedient and divergent synthetic route and preliminary SAR
Creators: Erin F DiMauro - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
John Newcomb - Department of HTS and Molecular Pharmacology, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Joseph J Nunes - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Jean E Bemis - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Christina Boucher - Department of HTS and Molecular Pharmacology, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
John L Buchanan - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
William H Buckner - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Alan Cheng - Amgen
Theodore Faust - Department of HTS and Molecular Pharmacology, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Faye Hsieh - Department of Pharmacokinetics and Drug Metabolism, Amgen Inc., One Amgen Center Drive, Thousand Oaks, CA 91320, USA
Xin Huang - Department of Molecular Structure, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Josie H Lee - Department of HTS and Molecular Pharmacology, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Teresa L Marshall - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Matthew W Martin - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
David C McGowan - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Stephen Schneider - Department of HTS and Molecular Pharmacology, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Susan M Turci - Department of HTS and Molecular Pharmacology, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Ryan D White - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Xiaotian Zhu - Department of Molecular Structure, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Publication Details: Bioorganic & medicinal chemistry letters, Vol.17(8), pp.2305-2309
Publisher: Elsevier Ltd
Identifiers: 9924086297701921
Academic Unit: Rabb School of Continuing Studies, Division of Graduate Professional Studies
Language: English
Resource Type: Journal article

Discovery of 4-amino-5,6-biaryl-furo[2,3- d]pyrimidines as inhibitors of Lck: Development of an expedient and divergent synthetic route and preliminary SAR

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