Development of a highly selective EP2-receptor agonist. Part 1: identification of 16-hydroxy-17,17-trimethylene PGE2 derivatives.
Design and synthesis of an EP2-receptor selective agonist began with the chemical modification of alpha- and omega-chains of butaprost 1a, which exhibits an affinity for the IP-receptor. Two series of prostaglandin (PG) analogues with a 16-hydroxy-17,17-trimethylene moiety as an omega-chain were identified. Among those tested, 4a,b,e,f,h and 6a,b,e,f,h were found to be highly selective EP2-receptor agonists. Structure-activity relationships are discussed.
Tani
Kousuke
K
Minase Research Institute, Ono Pharmaceutical Co., Ltd., Shimamoto, Mishima, 618-8585, Osaka, Japan. k.tani@ono.co.jp
Naganawa
Atsushi
A
Ishida
Akiharu
A
Sagawa
Kenji
K
Harada
Hiroyuki
H
Ogawa
Mikio
M
Maruyama
Takayuki
T
Ohuchida
Shuichi
S
Nakai
Hisao
H
Kondo
Kigen
K
Toda
Masaaki
M
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D015232:Dinoprostone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D011485:Protein Binding; D011869:Radioligand Assay; D018078:Receptors, Prostaglandin E / Q000819:agonists* / Q000378:metabolism; D058307:Receptors, Prostaglandin E, EP2 Subtype; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D000242:Cyclic AMP; D015232:Dinoprostone