Discovery of diphenylcarbamate derivatives as highly potent and selective IP receptor agonists: orally active prostacyclin mimetics. Part 3

  • Bioorg Med Chem Lett. 2005 Jun 15;15(12):3091-5. doi: 10.1016/j.bmcl.2005.04.047.
Kouji Hattori  1 ,  Akira Tanaka ,  Osamu Okitsu ,  Seiichiro Tabuchi ,  Kiyoshi Taniguchi ,  Mie Nishio ,  Satoshi Koyama ,  Masahide Higaki ,  Jiro Seki ,  Kazuo Sakane
Affiliations
  • 1. Medicinal Chemistry Research Laboratories, Fujisawa Pharmaceutical Co., Ltd, 2-1-6 Kashima, Yodogawa-ku, Osaka 532-8514, Japan. [email protected]
PMID: 15914004 DOI: 10.1016/j.bmcl.2005.04.047
Abstract

The new classes of diphenylcarbamate derivatives with a tetrahydronaphthalene skeleton as highly potent and selective IP agonists have been discovered. The optimized diphenylcarbamate type compound FK-788: (R)-4 exhibited potent antiaggregative potency with an IC50 of 18 nM and high binding affinity for the human recombinant IP receptor with K(i) values of 20 nM and selectivity for human IP over all Other members of the human prostanoid receptor family. Compound (R)-4 was shown to exhibit good pharmacokinetic properties in rats and dogs, and also good bioavailability in healthy volunteers.

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