Discovery of a novel indole series of EP1 receptor antagonists by scaffold hopping.
We describe the medicinal chemistry approach that generated a novel indole series of EP(1) receptor antagonists. The SAR of this new template was evaluated and culminated in the identification of compound 12g which demonstrated in vivo efficacy in a preclinical model of inflammatory pain.
Hall
Adrian
A
Neurology Centre of Excellence for Drug Discovery, GlaxoSmithKline, New Frontiers Science Park, Third Avenue, Harlow, Essex CM19 5AW, United Kingdom. adrian.2.hall@gsk.com
Billinton
Andy
A
Brown
Susan H
SH
Chowdhury
Anita
A
Giblin
Gerard M P
GM
Goldsmith
Paul
P
Hurst
David N
DN
Naylor
Alan
A
Patel
Sadhana
S
Scoccitti
Tiziana
T
Theobald
Pamela J
PJ
D000818:Animals; D006801:Humans; D006860:Hydrogen Bonding; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D058306:Receptors, Prostaglandin E, EP1 Subtype; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry
D007211:Indoles; C545635:PTGER1 protein, human; D018078:Receptors, Prostaglandin E; D058306:Receptors, Prostaglandin E, EP1 Subtype; D013844:Thiazoles; C030374:indole