Metabolism investigation leading to novel drug design 2: orally active prostacyclin mimetics. Part 5.
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.
Takamura
Fujiko
F
Biopharmaceutical and Pharmacokinetic Research Laboratories, Fujisawa Pharmaceutical Co., Yodogawa-ku, Osaka, Japan.
Tanaka
Akira
A
Takasugi
Hisashi
H
Taniguchi
Kiyoshi
K
Nishio
Mie
M
Seki
Jiro
J
Hattori
Kouji
K
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
D011464:Epoprostenol