Discovery of novel 2,3-diarylfuro[2,3-b]pyridin-4-amines as potent and selective inhibitors of Lck: synthesis, SAR, and pharmacokinetic properties

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

doi:10.1016/j.bmcl.2007.01.048

Discovery of novel 2,3-diarylfuro[2,3-b]pyridin-4-amines as potent and selective inhibitors of Lck: synthesis, SAR, and pharmacokinetic properties

Bioorg Med Chem Lett. 2007 Apr 15;17(8):2299-304. doi: 10.1016/j.bmcl.2007.01.048. Epub 2007 Jan 24.

Authors

Matthew W Martin¹, John Newcomb, Joseph J Nunes, Jean E Bemis, David C McGowan, Ryan D White, John L Buchanan, Erin F DiMauro, Christina Boucher, Theodore Faust, Faye Hsieh, Xin Huang, Josie H Lee, Stephen Schneider, Susan M Turci, Xiaotian Zhu

Affiliation

¹ Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA. matmarti@amgen.com

PMID: 17276681
DOI: 10.1016/j.bmcl.2007.01.048

Abstract

2,3-Diarylfuro[2,3-b]pyridine-4-amines are a novel class of potent and selective inhibitors of Lck. The discovery, synthesis, and structure activity relationships of this series of inhibitors are reported. The most promising compounds were also profiled to deduce their pharmacokinetic properties.

MeSH terms

Amines / chemical synthesis
Amines / pharmacokinetics
Animals
Humans
Inhibitory Concentration 50
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / antagonists & inhibitors*
Pharmacokinetics
Protein Kinase Inhibitors / chemical synthesis
Protein Kinase Inhibitors / pharmacokinetics
Pyridines / chemical synthesis*
Pyridines / pharmacokinetics*
Rats
Rats, Sprague-Dawley
Structure-Activity Relationship

Substances

Amines
Protein Kinase Inhibitors
Pyridines
Lymphocyte Specific Protein Tyrosine Kinase p56(lck)