Comparison between two classes of selective EP(3) antagonists and their biological activities.
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.
Belley
Michel
M
Merck Frosst Centre for Therapeutic Research, PO Box 1005, Pointe Claire-Dorval, Que., Canada H9R 4P8. belley@merck.com
Chan
Chi Chung
CC
Gareau
Yves
Y
Gallant
Michel
M
Juteau
Hélène
H
Houde
Karine
K
Lachance
Nicolas
N
Labelle
Marc
M
Sawyer
Nicole
N
Tremblay
Nathalie
N
Lamontagne
Sonia
S
Carrière
Marie-Claude
MC
Denis
Danielle
D
Greig
Gillian M
GM
Slipetz
Deborah
D
Gordon
Robert
R
Chauret
Nathalie
N
Li
Chun
C
Zamboni
Robert J
RJ
Metters
Kathleen M
KM
D002934:Cinnamates / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors*; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
D002934:Cinnamates; D018078:Receptors, Prostaglandin E; D013449:Sulfonamides