Discovery of 4-[1-[([1-[4-(trifluoromethyl)benzyl]-1H-indol-7-yl]carbonyl)amino]cyclopropyl]benzoic acid (MF-766), a highly potent and selective EP4 antagonist for treating inflammatory pain.
The discovery of a highly potent and selective EP(4) antagonist MF-766 is discussed. This N-benzyl indole derivative exhibits good pharmacokinetic profile and unprecedented in vivo potency in the rat AIA model.
Colucci
John
J
Department of Medicinal Chemistry, Merck Frosst Canada Ltd, Kirkland, Quebec, Canada.
Boyd
Michael
M
Berthelette
Carl
C
Chiasson
Jean-Francois
JF
Wang
Zhaoyin
Z
Ducharme
Yves
Y
Friesen
Rick
R
Wrona
Mark
M
Levesque
Jean-Francois
JF
Denis
Danielle
D
Mathieu
Marie-Claude
MC
Stocco
Rino
R
Therien
Alex G
AG
Clarke
Patsy
P
Rowland
Steve
S
Xu
Daigen
D
Han
Yongxin
Y
D000818:Animals; D001168:Arthritis / Q000188:drug therapy; D001565:Benzoates / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D002478:Cells, Cultured; D004285:Dogs; D055808:Drug Discovery; D004355:Drug Stability; D022781:Hepatocytes; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D007249:Inflammation / Q000188:drug therapy; D010146:Pain / Q000188:drug therapy*; D010599:Pharmacokinetics; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013329:Structure-Activity Relationship
D001565:Benzoates; D007211:Indoles; C545650:PTGER4 protein, human; C545652:Ptger4 protein, rat; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype