Design and synthesis of a highly selective EP4-receptor agonist. Part 1: 3,7-dithiaPG derivatives with high selectivity.
A series of 3,7-dithiaPGE(1) analogues 3, 4, 11, 16 and 19 were identified as highly selective EP4-receptor agonists starting from the chemical modification of 7-thiaPGE(1) analogue 1. EP4-receptor selectivity and agonist activity were maximized in 3 and 4.
Maruyama
T
T
Minase Research Institute, Ono Pharmaceutical Co., Ltd., Shimamoto, Mishima, 618-8585, Osaka, Japan. to.maruyama@ono.co.jp
Asada
M
M
Shiraishi
T
T
Ishida
A
A
Egashira
H
H
Yoshida
H
H
Maruyama
T
T
Ohuchida
S
S
Nakai
H
H
Kondo
K
K
Toda
M
M
D000475:Alkenes / Q000138:chemical synthesis* / Q000494:pharmacology*; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells / Q000378:metabolism; D006224:Cricetinae; D000242:Cyclic AMP / Q000819:agonists*; D003517:Cyclopentanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D015195:Drug Design; D006801:Humans; D008024:Ligands; D051379:Mice; D018078:Receptors, Prostaglandin E / Q000819:agonists*; D058309:Receptors, Prostaglandin E, EP4 Subtype; D012680:Sensitivity and Specificity; D013455:Sulfur / Q000737:chemistry*
D000475:Alkenes; D003517:Cyclopentanes; D008024:Ligands; C545650:PTGER4 protein, human; C545651:Ptger4 protein, mouse; D018078:Receptors, Prostaglandin E; D058309:Receptors, Prostaglandin E, EP4 Subtype; D013455:Sulfur; D000242:Cyclic AMP