Design and synthesis of a highly selective EP2-receptor agonist.
EP2-receptor selective agonist 3 was identified by the structural hybridization of butaprost 1a and PGE(2) 2a. Based on this information, a chemically more stabilized 4 was discovered as another highly selective EP2-receptor agonist, iv administration of which to anesthetized rats suppressed uterine motility, while PGE(2) 2a stimulated uterine motility.
Tani
K
K
Minase Research Institute, Ono Pharmaceutical Co., Ltd., Shimamoto, Mishima, 618-8585, Osaka, Japan. k.tani@ono.co.jp
Naganawa
A
A
Ishida
A
A
Egashira
H
H
Sagawa
K
K
Harada
H
H
Ogawa
M
M
Maruyama
T
T
Ohuchida
S
S
Nakai
H
H
Kondo
K
K
Toda
M
M
D000527:Alprostadil / Q000031:analogs & derivatives* / Q000138:chemical synthesis; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D016466:CHO Cells / Q000378:metabolism; D006224:Cricetinae; D000242:Cyclic AMP / Q000819:agonists; D003503:Cyclobutanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D015232:Dinoprostone / Q000378:metabolism / Q000494:pharmacology; D015195:Drug Design; D005260:Female; D006801:Humans; D008024:Ligands; D051379:Mice; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000819:agonists*; D058307:Receptors, Prostaglandin E, EP2 Subtype; D012680:Sensitivity and Specificity; D014590:Uterine Contraction / Q000187:drug effects*
D003503:Cyclobutanes; D003517:Cyclopentanes; D008024:Ligands; C545644:PTGER2 protein, human; C545645:Ptger2 protein, mouse; D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D000242:Cyclic AMP; D000527:Alprostadil; C048491:butaprost; D015232:Dinoprostone