Discovery of a potent and selective agonist of the prostaglandin EP4 receptor.
Analogues of PGE(2) wherein the hydroxycyclopentanone ring has been replaced by a lactam have been prepared and evaluated as ligands for the EP(4) receptor. An optimized compound (19a) shows high potency and agonist efficacy at the EP(4) receptor and is highly selective over the other seven known prostaglandin receptors.
Billot
Xavier
X
Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Québec, Canada H9R 4P8.
Chateauneuf
Anne
A
Chauret
Nathalie
N
Denis
Danielle
D
Greig
Gillian
G
Mathieu
Marie Claude
MC
Metters
Kathleen M
KM
Slipetz
Deborah M
DM
Young
Robert N
RN
D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology*; D015195:Drug Design; D006207:Half-Life; D006801:Humans; D007202:Indicators and Reagents; D011760:Pyrrolidinones / Q000138:chemical synthesis / Q000494:pharmacology*; D018078:Receptors, Prostaglandin E / Q000819:agonists*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013777:Tetrazoles / Q000138:chemical synthesis / Q000494:pharmacology*
C000598602:CAY10598; D007202:Indicators and Reagents; C545650:PTGER4 protein, human; D011760:Pyrrolidinones; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013777:Tetrazoles; D015232:Dinoprostone