title: Replacing the cyclohexene-linker of FR181157 leading to novel IP receptor agonists: orally active prostacyclin mimetics. Part 6.
abstract: The synthesis and biological activity of novel derivatives of our previously reported IP receptor agonist FR181157 is described. SAR studies to replace the cyclohexene-linker of FR181157 led to the discovery of compound 1i (FR207845) as a potent non-prostanoid PGI2 mimetic with good oral bioavailability.
authors.affiliation: Chemistry Research Laboratories, Astellas Pharma Inc., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan. akira-tanaka@jp.astellas.com
authors.forename: Akira
authors.initials: A
authors.lastname: Tanaka
authors.forename: Kouji
authors.initials: K
authors.lastname: Hattori
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Osamu
authors.initials: O
authors.lastname: Okitsu
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Tabuchi
authors.forename: Mie
authors.initials: M
authors.lastname: Nishio
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Nagakura
authors.forename: Noriaki
authors.initials: N
authors.lastname: Maeda
authors.forename: Hidetsugu
authors.initials: H
authors.lastname: Murai
authors.forename: Jiro
authors.initials: J
authors.lastname: Seki
mesh_terms: D000284:Administration, Oral; D000818:Animals; D032701:Biomimetics; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003510:Cyclohexanes / Q000737:chemistry*; D053138:Cyclohexenes; D011464:Epoprostenol / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D015394:Molecular Structure; D010080:Oxazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects; D051381:Rats; D011982:Receptors, Prostaglandin / Q000819:agonists*; D013329:Structure-Activity Relationship
chemical_list: D003432:Cross-Linking Reagents; D003510:Cyclohexanes; D053138:Cyclohexenes; D010080:Oxazoles; D011982:Receptors, Prostaglandin; C052568:cyclohexene; C488220:FR181157; D011464:Epoprostenol