title: Metabolism investigation leading to novel drug design 2: orally active prostacyclin mimetics. Part 5.
abstract: A metabolism study of FK788 (2) led to the discovery of new diphenylcarbamoyl derivatives as prostacyclin mimetics without the PG skeleton. We designed and evaluated PGI(2) mimetics based on blocking the main metabolic pathway of FK788. The new compound 7c was found to be equipotent to FK788 towards PGI(2) agonist activity and metabolically more stable than FK788.
authors.affiliation: Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Yodogawa-ku, Osaka, Japan.
authors.forename: Fujiko
authors.initials: F
authors.lastname: Takamura
authors.forename: Akira
authors.initials: A
authors.lastname: Tanaka
authors.forename: Hisashi
authors.initials: H
authors.lastname: Takasugi
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Taniguchi
authors.forename: Mie
authors.initials: M
authors.lastname: Nishio
authors.forename: Jiro
authors.initials: J
authors.lastname: Seki
authors.forename: Kouji
authors.initials: K
authors.lastname: Hattori
mesh_terms: D000284:Administration, Oral; D000818:Animals; D032701:Biomimetics; D004195:Disease Models, Animal; D015195:Drug Design; D011464:Epoprostenol / Q000008:administration & dosage / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D006801:Humans; D008099:Liver / Q000187:drug effects / Q000293:injuries / Q000378:metabolism; D008861:Microsomes / Q000187:drug effects; D015394:Molecular Structure; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D011464:Epoprostenol