Discovery of a series of acrylic acids and their derivatives as chemical leads for selective EP3 receptor antagonists.
A series of acrylic acids and their structurally related compounds were evaluated for their binding affinity to four EP receptor subtypes (EP1-4). Starting from the initial hit 3, which was discovered in our in-house library, compounds 4 and 5 were identified as new chemical leads as candidates for further optimization towards a selective EP3 receptor antagonist. The identification process of these compounds and their pharmacokinetic profiles are presented.
Asada
Masaki
M
Minase Research Institute, Ono Pharmaceutical Co., Ltd, Shimamoto, Mishima, Osaka 618-8585, Japan. m.asada@ono.co.jp
Obitsu
Tetsuo
T
Nagase
Toshihiko
T
Sugimoto
Isamu
I
Yamaura
Yoshiyuki
Y
Sato
Kazutoyo
K
Narita
Masami
M
Ohuchida
Shuichi
S
Nakai
Hisao
H
Toda
Masaaki
M
D000179:Acrylates / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D051379:Mice; D008862:Microsomes, Liver / Q000378:metabolism; D015394:Molecular Structure; D011485:Protein Binding; D011720:Pyrazoles / Q000737:chemistry*; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D058308:Receptors, Prostaglandin E, EP3 Subtype; D013329:Structure-Activity Relationship
D000179:Acrylates; C545647:PTGER3 protein, human; C545648:Ptger3 protein, mouse; D011720:Pyrazoles; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; C031280:pyrazole; C036658:acrylic acid