Discovery of novel 2,3-diarylfuro[2,3-b]pyridin-4-amines as potent and selective inhibitors of Lck: synthesis, SAR, and pharmacokinetic properties.
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.
Martin
Matthew W
MW
Department of Medicinal Chemistry, Amgen Inc., One Kendall Square, Building 1000, Cambridge, MA 02139, USA. matmarti@amgen.com
Newcomb
John
J
Nunes
Joseph J
JJ
Bemis
Jean E
JE
McGowan
David C
DC
White
Ryan D
RD
Buchanan
John L
JL
DiMauro
Erin F
EF
Boucher
Christina
C
Faust
Theodore
T
Hsieh
Faye
F
Huang
Xin
X
Lee
Josie H
JH
Schneider
Stephen
S
Turci
Susan M
SM
Zhu
Xiaotian
X
D000588:Amines / Q000138:chemical synthesis / Q000493:pharmacokinetics; D000818:Animals; D006801:Humans; D020128:Inhibitory Concentration 50; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck) / Q000037:antagonists & inhibitors*; D010599:Pharmacokinetics; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000493:pharmacokinetics; D011725:Pyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship
D000588:Amines; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D019860:Lymphocyte Specific Protein Tyrosine Kinase p56(lck)