Comparison between two classes of selective EP3 antagonists and their biological activities

被引：31

作者：

Belley, Michel ^{[1
]}

Chan, Chi Chung ^{[1
]}

Gareau, Yves ^{[1
]}

Gallant, Michel ^{[1
]}

Juteau, Helene ^{[1
]}

Houde, Karine ^{[1
]}

Lachance, Nicolas ^{[1
]}

Labelle, Marc ^{[1
]}

Sawyer, Nicole ^{[1
]}

Tremblay, Nathalie ^{[1
]}

Lamontagne, Sonia ^{[1
]}

Carriere, Marie-Claude ^{[1
]}

Denis, Danielle ^{[1
]}

Greig, Gillian M. ^{[1
]}

Slipetz, Deborah ^{[1
]}

Gordon, Robert ^{[1
]}

Chauret, Nathalie ^{[1
]}

Li, Chun ^{[1
]}

Zamboni, Robert J. ^{[1
]}

Metters, Kathleen M. ^{[1
]}

机构：

[1] Merck Frosst Ctr Therapeut Res, Pointe Claire, PQ H9R 4P8, Canada

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 21期

关键词：

EP3; antagonist; acylsulfonamides; cinnamic acids; metabolism; rat paw edema; rat paw hyperalgesia; anti-inflammation; analgesic;

D O I：

10.1016/j.bmcl.2006.08.025

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Two different series of very potent and selective EP3 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., Carriere, 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., Carriere, M.-C., Denis, D., Metters, K. M. Bioorg. Med. Chem. 2001, 9, 1977; (b) Juteau, H., Gareau, Y., Labelle, M., Lamontagne, S., Tremblay, N., Carriere, 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 EP3 receptor. (c) 2006 Elsevier Ltd. All rights reserved.

引用

页码：5639 / 5642

页数：4

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