Comparison between two classes of selective EP(3) antagonists and their biological activities

• Published in: Bioorganic & medicinal chemistry letters Vol. 16; no. 21; pp. 5639 - 5642
• Main Authors: Belley, Michel, Chan, Chi Chung, Gareau, Yves, Gallant, Michel, Juteau, Hélène, Houde, Karine, Lachance, Nicolas, Labelle, Marc, Sawyer, Nicole, Tremblay, Nathalie, Lamontagne, Sonia, Carrière, Marie-Claude, Denis, Danielle, Greig, Gillian M, Slipetz, Deborah, Gordon, Robert, Chauret, Nathalie, Li, Chun, Zamboni, Robert J, Metters, Kathleen M
• Format: Journal Article
• Language: English
• Published: England 01-11-2006
• Subjects: Cinnamates - chemistry; Cinnamates - pharmacology; Humans; Receptors, Prostaglandin E - antagonists & inhibitors; Sulfonamides - chemistry; Sulfonamides - pharmacology
• ISSN: 0960-894X

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.