Structure-activity relationship of cinnamic acylsulfonamide analogues on the human EP3 prostanoid receptor.
Potent and selective antagonists of the human EP3 receptor have been identified. The structure-activity relationship of the chemical series was conducted and we found several analogues displaying sub-nanomolar K(i) values at the EP3 receptor and micromolar activities at the EP1, EP2 and EP4 receptors. The effect of added human serum albumin (HSA) on the binding affinity at the EP3 receptor was also investigated.
Juteau
H
H
Merck Frosst Canada & Co., Pointe-Claire-Dorval, H9R 4P8, Québec, Canada.
Gareau
Y
Y
Labelle
M
M
Sturino
C F
CF
Sawyer
N
N
Tremblay
N
N
Lamontagne
S
S
Carrière
M C
MC
Denis
D
D
Metters
K M
KM
D002934:Cinnamates / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D011448:Prostaglandin Antagonists / Q000737:chemistry / Q000494:pharmacology*; D018078:Receptors, Prostaglandin E / Q000187:drug effects / Q000378:metabolism*; D058308:Receptors, Prostaglandin E, EP3 Subtype; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry / Q000494:pharmacology*
D002934:Cinnamates; C545647:PTGER3 protein, human; D011448:Prostaglandin Antagonists; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D013449:Sulfonamides