Replacing the cyclohexene-linker of FR181157 leading to novel IP receptor agonists: orally active prostacyclin mimetics. Part 6.
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.
Tanaka
Akira
A
Chemistry Research Laboratories, Astellas Pharma Inc., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan. akira-tanaka@jp.astellas.com
Hattori
Kouji
K
Taniguchi
Kiyoshi
K
Okitsu
Osamu
O
Tabuchi
Seiichiro
S
Nishio
Mie
M
Nagakura
Yasunori
Y
Maeda
Noriaki
N
Murai
Hidetsugu
H
Seki
Jiro
J
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
D003432:Cross-Linking Reagents; D003510:Cyclohexanes; D053138:Cyclohexenes; D010080:Oxazoles; D011982:Receptors, Prostaglandin; C052568:cyclohexene; C488220:FR181157; D011464:Epoprostenol