Author/Authors :
Michel Belley، نويسنده , , Chi-Chung Chan، نويسنده , , Yves Gareau، نويسنده , , Michel Gallant، نويسنده , , Hélène Juteau، نويسنده , , Karine Houde، نويسنده , , Nicolas Lachance، نويسنده , , Marc Labelle، نويسنده , , Nicole Sawyer، نويسنده , , Nathalie Tremblay، نويسنده , , Sonia Lamontagne، نويسنده , , Marie-Claude Carrière، نويسنده , , Danielle Denis، نويسنده , , Gillian M. Greig، نويسنده , , Deborah Slipetz، نويسنده , , Robert Gordon، نويسنده , , Nathalie Chauret، نويسنده , , Chun Li، نويسنده , , Robert J. Zamboni، نويسنده , , Kathleen M. Metters، نويسنده ,
Abstract :
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., 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 Ki as low as 0.6 nM on the EP3 receptor.
