A simple stereoselective synthesis and biological evaluation of FR181157: orally active prostacyclin mimetic.
Synthetic method of a novel prostaglandin (PG) mimetic: FR181175 without PG skeleton are described. The key to success is creation of a chiral epoxide using Sharpless AD reaction with high ee yield. FR181157 shows high potency and agonist efficacy at the IP receptor and has good bioavailability.
Hattori
Kouji
K
Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceutical Co. Ltd, 1-6, Kashima 2-Chome, Yodogawa-Ku, Osaka, Japan. kouji_hattori@po.fujisawa.co.jp
Tabuchi
Seiichiro
S
Okitsu
Osamu
O
Taniguchi
Kiyoshi
K
D000284:Administration, Oral; D000818:Animals; D019540:Area Under Curve; D011464:Epoprostenol / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D005215:Fasting; D008958:Models, Molecular; D008968:Molecular Conformation; D010080:Oxazoles / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D010080:Oxazoles; C488220:FR181157; D011464:Epoprostenol