Discovery of sodium 6-[(5-chloro-2-{[(4-chloro-2-fluorophenyl)methyl]oxy}phenyl)methyl]-2-pyridinecarboxylate (GSK269984A) an EP(1) receptor antagonist for the treatment of inflammatory pain.
We describe the medicinal chemistry programme that led to the identification of the EP(1) receptor antagonist GSK269984A (8h). GSK269984A was designed to overcome development issues encountered with previous EP(1) antagonists such as GW848687X and was found to display excellent activity in preclinical models of inflammatory pain. However, upon cross species pharmacokinetic profiling, GSK269984A was predicted to have suboptimal human pharmacokinetic and was thus progressed to a human microdose study.
Hall
Adrian
A
Neurosciences Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex, CM19 5AW, UK.
Billinton
Andy
A
Brown
Susan H
SH
Chowdhury
Anita
A
Clayton
Nicholas M
NM
Giblin
Gerard M P
GM
Gibson
Mairi
M
Goldsmith
Paul A
PA
Hurst
David N
DN
Naylor
Alan
A
Peet
Caroline F
CF
Scoccitti
Tiziana
T
Wilson
Alexander W
AW
Winchester
Wendy
W