title: Structure-activity relationship studies on ortho-substituted cinnamic acids, a new class of selective EP(3) antagonists.
abstract: A series of novel ortho-substituted cinnamic acids have been synthesized, and their binding activity and selectivity on the four prostaglandin E(2) receptors evaluated. Many of them are very potent and selective EP(3) antagonists (K(i) 3-10 nM), while compound 9 is a very good and selective EP(2) agonist (K(i) 8 nM). The biological profile of the EP(2) agonist 9 in vivo and the metabolic profile of selected EP(3) antagonists are also reported.
authors.affiliation: Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Québec, Canada H9R 4P8. belley@merck.com
authors.forename: Michel
authors.initials: M
authors.lastname: Belley
authors.forename: Michel
authors.initials: M
authors.lastname: Gallant
authors.forename: Bruno
authors.initials: B
authors.lastname: Roy
authors.forename: Karine
authors.initials: K
authors.lastname: Houde
authors.forename: Nicolas
authors.initials: N
authors.lastname: Lachance
authors.forename: Marc
authors.initials: M
authors.lastname: Labelle
authors.forename: Laird A
authors.initials: LA
authors.lastname: Trimble
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chauret
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: Nicole
authors.initials: N
authors.lastname: Sawyer
authors.forename: Nathalie
authors.initials: N
authors.lastname: Tremblay
authors.forename: Sonia
authors.initials: S
authors.lastname: Lamontagne
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Carrière
authors.forename: Danielle
authors.initials: D
authors.lastname: Denis
authors.forename: Gillian M
authors.initials: GM
authors.lastname: Greig
authors.forename: Deborah
authors.initials: D
authors.lastname: Slipetz
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Metters
authors.forename: Robert
authors.initials: R
authors.lastname: Gordon
authors.forename: Chi Chung
authors.initials: CC
authors.lastname: Chan
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Zamboni
mesh_terms: D002460:Cell Line; D002934:Cinnamates / Q000138:chemical synthesis* / Q000378:metabolism / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis; D006801:Humans; D010599:Pharmacokinetics; D011485:Protein Binding; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D013329:Structure-Activity Relationship
chemical_list: D002934:Cinnamates; C545644:PTGER2 protein, human; C545647:PTGER3 protein, human; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D058308:Receptors, Prostaglandin E, EP3 Subtype; D000242:Cyclic AMP