The identification of pyrazolo[1,5-a]pyridines as potent p38 kinase inhibitors.
A series of pyrazolo[1,5-a]pyridine derivatives was designed and synthesized as novel potent p38 kinase inhibitors. Our approaches towards improving in vitro metabolism and in vivo pharmacokinetic properties of the series are described.
Cheung
Mui
M
GlaxoSmithKline, Five Moore Drive, Research Triangle Park, NC 27709, USA. mui.h.cheung@gsk.com
Harris
Philip A
PA
Badiang
Jennifer G
JG
Peckham
Gregory E
GE
Chamberlain
Stanley D
SD
Alberti
Michael J
MJ
Jung
David K
DK
Harris
Stephanie S
SS
Bramson
Neal H
NH
Epperly
Andrea H
AH
Stimpson
Stephen A
SA
Peel
Michael R
MR
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology; D019540:Area Under Curve; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D004285:Dogs; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000493:pharmacokinetics*; D006801:Humans; D020128:Inhibitory Concentration 50; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D020935:MAP Kinase Signaling System; D011725:Pyridines / Q000138:chemical synthesis* / Q000493:pharmacokinetics; D051381:Rats; D013329:Structure-Activity Relationship; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D004791:Enzyme Inhibitors; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases