Discovery of novel prostaglandin analogs of PGE2 as potent and selective EP2 and EP4 receptor agonists.
Analogs of PGE(2) with introduction of diene groups at the omega-side chain have been synthesized and evaluated for their binding affinity for EP(2) and EP(4) receptors. An optimized analog (compound 9b) showed high potency and selectivity for the EP(4) receptor over other known receptors.
Xiao
Yufang
Y
Department of Medicinal Chemistry, EMD Serono Research Institute, Inc., Rockland, MA 02370, USA. yufang.xiao@emdserono.com
Araldi
Gian Luca
GL
Zhao
Zhong
Z
Brugger
Nadia
N
Karra
Srinivasa
S
Fischer
David
D
Palmer
Elizabeth
E
D000818:Animals; D002460:Cell Line; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000493:pharmacokinetics / Q000494:pharmacology; D006207:Half-Life; D006801:Humans; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000819:agonists*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype
C545644:PTGER2 protein, human; C545650:PTGER4 protein, human; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058309:Receptors, Prostaglandin E, EP4 Subtype; D015232:Dinoprostone