title: Comparison between two classes of selective EP(3) antagonists and their biological activities.
abstract: Two different series of very potent and selective EP(3) antagonists have been reported: a novel series of ortho-substituted cinnamic acids [Belley, M., Gallant, M., Roy, B., Houde, K., Lachance, N., Labelle, M., Trimble, L., Chauret, N., Li, C., Sawyer, N., Tremblay, N., Lamontagne, S., Carrière, M.-C., Denis, D., Greig, G. M., Slipetz, D., Metters, K. M., Gordon, R., Chan, C. C., Zamboni, R. J. Bioorg. Med. Chem. Lett.2005, 15, 527] and the acylsulfonamides of ortho-(arylmethyl)cinnamates. [(a) Juteau, H., Gareau, Y., Labelle, M., Sturino, C. F., Sawyer, N., Tremblay, N., Lamontagne, S., Carrière, M.-C., Denis, D., Metters, K. M. Bioorg. Med. Chem. 2001, 9, 1977; (b) Juteau, H., Gareau, Y., Labelle, M., Lamontagne, S., Tremblay, N., Carrière, M.-C., Denis, D., Sawyer, N., Metters, K. M. Bioorg. Med. Chem. Lett.2001, 11, 747] The structural differences between the two series, along with their biological activity in vivo, in vitro, and metabolism, are analyzed. Some of those compounds, including hybrids containing the best structural features of both series, possess K(i) as low as 0.6 nM on the EP(3) receptor.
authors.affiliation: Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Que., Canada H9R 4P8. belley@merck.com
authors.forename: Michel
authors.initials: M
authors.lastname: Belley
authors.forename: Chi Chung
authors.initials: CC
authors.lastname: Chan
authors.forename: Yves
authors.initials: Y
authors.lastname: Gareau
authors.forename: Michel
authors.initials: M
authors.lastname: Gallant
authors.forename: Hélène
authors.initials: H
authors.lastname: Juteau
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: 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: Robert
authors.initials: R
authors.lastname: Gordon
authors.forename: Nathalie
authors.initials: N
authors.lastname: Chauret
authors.forename: Chun
authors.initials: C
authors.lastname: Li
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Zamboni
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Metters
mesh_terms: D002934:Cinnamates / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D002934:Cinnamates; D018078:Receptors, Prostaglandin E; D013449:Sulfonamides