N-(3-(Phenylcarbamoyl)arylpyrimidine)-5-carboxamides as potent and selective inhibitors of Lck: Structure, synthesis and SAR

Holly L Deak; John R Newcomb; Joseph J Nunes; Christina Boucher; Alan C Cheng; Erin F DiMauro; Linda F Epstein; Paul Gallant; Brian L Hodous; Xin Huang; Josie H Lee; Vinod F Patel; Stephen Schneider; Susan M Turci; Xiaotian Zhu

doi:10.1016/j.bmcl.2007.11.123

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N-(3-(Phenylcarbamoyl)arylpyrimidine)-5-carboxamides as potent and selective inhibitors of Lck: Structure, synthesis and SAR

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N-(3-(Phenylcarbamoyl)arylpyrimidine)-5-carboxamides as potent and selective inhibitors of Lck: Structure, synthesis and SAR

Holly L Deak, John R Newcomb, Joseph J Nunes, Christina Boucher, Alan C Cheng, Erin F DiMauro, Linda F Epstein, Paul Gallant, Brian L Hodous, Xin Huang, …

Bioorganic & medicinal chemistry letters, Vol.18(3), pp.1172-1176

2008

DOI: https://doi.org/10.1016/j.bmcl.2007.11.123

PMID: 18083554

Abstract

Kinase inhibitor

Lck inhibitor

A novel class of selective Lck inhibitors is reported. X-ray co-crystal structural data, structure–activity relationships, and the synthesis of these inhibitors are described. N-3-(Phenylcarbamoyl)arylpyrimidine-5-carboxamides are a novel class of selective Lck inhibitors. This series of compounds derives its selectivity from a hydrogen bond with the gatekeeper Thr316 of the enzyme. X-ray co-crystal structural data, structure–activity relationships, and the synthesis of these inhibitors are reported herein.

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Title: N-(3-(Phenylcarbamoyl)arylpyrimidine)-5-carboxamides as potent and selective inhibitors of Lck: Structure, synthesis and SAR
Creators: Holly L Deak - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
John R Newcomb - Department of HTS & 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
Christina Boucher - Department of HTS & Molecular Pharmacology, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Alan C Cheng - Amgen
Erin F DiMauro - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Linda F Epstein - Department of Molecular Structure, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Paul Gallant - Department of HTS & Molecular Pharmacology, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Brian L Hodous - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Xin Huang - Department of Molecular Structure, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Josie H Lee - Department of HTS & Molecular Pharmacology, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Vinod F Patel - Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Stephen Schneider - Department of HTS & Molecular Pharmacology, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA
Susan M Turci - Department of HTS & Molecular Pharmacology, 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.18(3), pp.1172-1176
Publisher: Elsevier Ltd
Identifiers: 9924086778201921
Academic Unit: Rabb School of Continuing Studies, Division of Graduate Professional Studies
Language: English
Resource Type: Journal article

N-(3-(Phenylcarbamoyl)arylpyrimidine)-5-carboxamides as potent and selective inhibitors of Lck: Structure, synthesis and SAR

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