Structure-activity relationships of triazolopyridine oxazole p38 inhibitors: identification of candidates for clinical development.
The synthesis, structure-activity relationship, in vivo activity, and metabolic profile for a series of triazolopyridine-oxazole based p38 inhibitors are described. The deficiencies of the lead structure in the series, CP-808844, were overcome by changes to the C4 aryl group and the triazole side-chain culminating in the identification of several potential clinical candidates.
McClure
Kim F
KF
Pfizer Global Research and Development, Groton Laboratories, CT 06340, USA. kim.f.mcclure@pfizer.com
Letavic
Michael A
MA
Kalgutkar
Amit S
AS
Gabel
Christopher A
CA
Audoly
Laurent
L
Barberia
John T
JT
Braganza
John F
JF
Carter
Demetrius
D
Carty
Thomas J
TJ
Cortina
Santo R
SR
Dombroski
Mark A
MA
Donahue
Kathleen M
KM
Elliott
Nancy C
NC
Gibbons
Colleen P
CP
Jordan
Crystal K
CK
Kuperman
Alexander V
AV
Labasi
Jeff M
JM
Laliberte
Ronald E
RE
McCoy
Jennifer M
JM
Naiman
Brian M
BM
Nelson
Kendra L
KL
Nguyen
Hang T
HT
Peese
Kevin M
KM
Sweeney
Francis J
FJ
Taylor
Timothy J
TJ
Trebino
Catherine E
CE
Abramov
Yuriy A
YA
Laird
Ellen R
ER
Volberg
Walter A
WA
Zhou
Jun
J
Bach
Justin
J
Lombardo
Franco
F
D002626:Chemistry, Pharmaceutical; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007700:Kinetics; D008956:Models, Chemical; D010080:Oxazoles / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D012995:Solubility; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000737:chemistry; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors* / Q000737:chemistry*
D004791:Enzyme Inhibitors; D010080:Oxazoles; D011725:Pyridines; D014230:Triazoles; D048051:p38 Mitogen-Activated Protein Kinases