title: Development of a highly selective EP2-receptor agonist. Part 1: identification of 16-hydroxy-17,17-trimethylene PGE2 derivatives.
abstract: 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.
authors.affiliation: Minase Research Institute, Ono Pharmaceutical Co., Ltd., Shimamoto, Mishima, 618-8585, Osaka, Japan. k.tani@ono.co.jp
authors.forename: Kousuke
authors.initials: K
authors.lastname: Tani
authors.forename: Atsushi
authors.initials: A
authors.lastname: Naganawa
authors.forename: Akiharu
authors.initials: A
authors.lastname: Ishida
authors.forename: Kenji
authors.initials: K
authors.lastname: Sagawa
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Harada
authors.forename: Mikio
authors.initials: M
authors.lastname: Ogawa
authors.forename: Takayuki
authors.initials: T
authors.lastname: Maruyama
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ohuchida
authors.forename: Hisao
authors.initials: H
authors.lastname: Nakai
authors.forename: Kigen
authors.initials: K
authors.lastname: Kondo
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toda
mesh_terms: 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
chemical_list: D018078:Receptors, Prostaglandin E; D058307:Receptors, Prostaglandin E, EP2 Subtype; D000242:Cyclic AMP; D015232:Dinoprostone