Discovery of novel arylpyrazole series as potent and selective opioid receptor-like 1 (ORL1) antagonists

  • Bioorg Med Chem Lett. 2009 Jul 1;19(13):3627-31. doi: 10.1016/j.bmcl.2009.04.116.
Kensuke Kobayashi  1 ,  Minaho Uchiyama ,  Hirokatsu Ito ,  Hirobumi Takahashi ,  Takashi Yoshizumi ,  Hiroki Sakoh ,  Yasushi Nagatomi ,  Masanori Asai ,  Hiroshi Miyazoe ,  Tomohiro Tsujita ,  Mioko Hirayama ,  Satoshi Ozaki ,  Takeshi Tani ,  Yasuyuki Ishii ,  Hisashi Ohta ,  Osamu Okamoto
Affiliations
  • 1. Tsukuba Research Institute, Banyu Pharmaceutical Co., Ltd, Okubo-3, Tsukuba, Ibaraki 300-2611, Japan.
PMID: 19447610 DOI: 10.1016/j.bmcl.2009.04.116
Abstract

The synthesis and biological evaluation of new potent opioid receptor-like 1 antagonists are presented. A structure-activity relationship (SAR) study of arylpyrazole lead compound 1 obtained from library screening identified compound 31, (1S,3R)-N-{[1-(3-chloropyridin-2-yl)-5-(5-fluoro-6-methylpyridin-3-yl)-4-methyl-1H-pyrazol-3-yl]methyl}-3-fluorocyclopentanamine, which exhibits high intrinsic potency and selectivity against other opioid receptors and hERG Potassium Channel.

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