Identification and optimization of novel 1,3,4-oxadiazole EP1 receptor antagonists.
A novel series of oxadiazole EP1 receptor antagonists was identified by replacing the amide of a known glycine sulfonamide derivative with a 1,3,4-oxadiazole. Optimization of the substitution patterns on the three aromatic rings led to the identification of high affinity EP1 receptor antagonists. The derivative with highest affinity displayed a binding IC50 of 2.5 nM (pIC50 8.6).
Hall
Adrian
A
Neurology and Gastrointestinal Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, UK. adrian.2.hall@gsk.com
Brown
Susan H
SH
Chowdhury
Anita
A
Giblin
Gerard M P
GM
Gibson
Mairi
M
Healy
Mark P
MP
Livermore
David G
DG
Wilson
Richard J McArthur
RJ
Naylor
Alan
A
Rawlings
D Anthony
DA
Roman
Shilina
S
Ward
Emma
E
Willay
Caroline
C
D008958:Models, Molecular; D015394:Molecular Structure; D010069:Oxadiazoles / Q000737:chemistry* / Q000494:pharmacology*; D011485:Protein Binding; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D013329:Structure-Activity Relationship
D010069:Oxadiazoles; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype