title: 3-(2-Aminocarbonylphenyl)propanoic acid analogs as potent and selective EP3 receptor antagonists. Part 1: discovery and exploration of the carboxyamide side chain.
abstract: A series of 3-(2-aminocarbonyl-4-phenoxymethylphenyl)propanoic acid analogs were synthesized and evaluated for their EP3 antagonist activity in the presence of additive serum albumin. Several compounds were biologically evaluated for their in vivo efficacy with respect to the PGE(2)-induced uterine contraction in pregnant rats as well as their pharmacokinetics. The discovery process of these potent and selective EP3 antagonists and their structure activity relationship are also presented.
authors.affiliation: Minase Research Institute, Ono Pharmaceutical Co., Ltd, Shimamoto, Mishima, Osaka 618-8585, Japan. m.asada@ono.co.jp
authors.forename: Masaki
authors.initials: M
authors.lastname: Asada
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Obitsu
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Nagase
authors.forename: Motoyuki
authors.initials: M
authors.lastname: Tanaka
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Yamaura
authors.forename: Hiroya
authors.initials: H
authors.lastname: Takizawa
authors.forename: Ken
authors.initials: K
authors.lastname: Yoshikawa
authors.forename: Kazutoyo
authors.initials: K
authors.lastname: Sato
authors.forename: Masami
authors.initials: M
authors.lastname: Narita
authors.forename: Shuichi
authors.initials: S
authors.lastname: Ohuchida
authors.forename: Hisao
authors.initials: H
authors.lastname: Nakai
authors.forename: Masaaki
authors.initials: M
authors.lastname: Toda
mesh_terms: D000818:Animals; D016466:CHO Cells; D002417:Cattle; D006224:Cricetinae; D003412:Cricetulus; D005260:Female; D051379:Mice; D010647:Phenyl Ethers; D011247:Pregnancy; D011422:Propionates / Q000737:chemistry; D051381:Rats; D018078:Receptors, Prostaglandin E / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D058308:Receptors, Prostaglandin E, EP3 Subtype; D012710:Serum Albumin, Bovine / Q000378:metabolism; D014590:Uterine Contraction / Q000187:drug effects*
chemical_list: C548852:3-(2-aminocarbonyl-4-phenoxymethylphenyl)propanoic acid; D010647:Phenyl Ethers; D011422:Propionates; C545648:Ptger3 protein, mouse; D018078:Receptors, Prostaglandin E; D058308:Receptors, Prostaglandin E, EP3 Subtype; D012710:Serum Albumin, Bovine