Replacing the cyclohexene-linker of FR181157 leading to novel IP receptor agonists: orally active prostacyclin mimetics. Part 6

Akira Tanaka; Kouji Hattori; Kiyoshi Taniguchi; Osamu Okitsu; Seiichiro Tabuchi; Mie Nishio; Yasunori Nagakura; Noriaki Maeda; Hidetsugu Murai; Jiro Seki

doi:10.1016/j.bmcl.2006.06.076

Replacing the cyclohexene-linker of FR181157 leading to novel IP receptor agonists: orally active prostacyclin mimetics. Part 6

Bioorg Med Chem Lett. 2006 Sep 15;16(18):4861-4. doi: 10.1016/j.bmcl.2006.06.076. Epub 2006 Jul 11.

Authors

Akira Tanaka¹, Kouji Hattori, Kiyoshi Taniguchi, Osamu Okitsu, Seiichiro Tabuchi, Mie Nishio, Yasunori Nagakura, Noriaki Maeda, Hidetsugu Murai, Jiro Seki

Affiliation

¹ Chemistry Research Laboratories, Astellas Pharma Inc., 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan. akira-tanaka@jp.astellas.com

PMID: 16837197
DOI: 10.1016/j.bmcl.2006.06.076

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.

MeSH terms

Administration, Oral
Animals
Biomimetics
Cross-Linking Reagents / chemistry*
Cyclohexanes / chemistry*
Cyclohexenes
Epoprostenol / chemistry*
Epoprostenol / pharmacology*
Humans
Molecular Structure
Oxazoles / administration & dosage
Oxazoles / chemical synthesis
Oxazoles / chemistry*
Oxazoles / pharmacology*
Platelet Aggregation / drug effects
Rats
Receptors, Prostaglandin / agonists*
Structure-Activity Relationship

Substances

Cross-Linking Reagents
Cyclohexanes
Cyclohexenes
Oxazoles
Receptors, Prostaglandin
cyclohexene
FR181157
Epoprostenol