Discovery of Gemilukast (ONO-6950), a Dual CysLT<sub>1</sub> and CysLT<sub>2</sub> Antagonist

DOI
  • Itadani Satoshi
    CMC Management CMC & Production Strategy Development CMC & Production HQs, Ono Pharmaceutical Co., Ltd.
  • Takeuchi Jun
    Medicinal Chemistry Research Laboratories, Ono Pharmaceutical Co., Ltd.
  • Ohmoto Kazuyuki
    IP Strategy, Ono Pharmaceutical Co., Ltd.

Bibliographic Information

Other Title
  • Dual CysLT<sub>1</sub>/CysLT<sub>2</sub>受容体拮抗薬—Gemilukast（ONO-6950）の創製—

Abstract

<p>Several CysLT1 antagonists are widely used in clinical as a therapeutic agent for treating bronchial asthma and allergic rhinitis, because of their high potency and high safety as well. On the other hand, some patients are reported not to respond clinically. It is not known exactly why such nonresponders exist. Nonetheless, several reports say that CysLT2 receptor, identified as another leukotriene receptor, can involve airways contraction and inflammation. Therefore, we hypothesized that dual CysLT1 /CysLT2 antagonists can be more potent and useful therapeutic agents for asthma, and then started drug discovery research from our hit compounds possessing both CysLT1 and CysLT2 antagonist activities. After a variety of drug designs and syntheses, we discovered gemilukast (ONO-6950, compound 26) showing potent dual CysLT1/CysLT2 antagonist activities. Gemilukast is currently being evaluated in phase II trials for the treatment of asthma. In this report, we describe the development of gemilukast including details of structure-activity relationships and pharmacokinetics evaluations.</p>

Journal

  • MEDCHEM NEWS

    MEDCHEM NEWS 26 (3), 138-146, 2016-08-01

    The Pharmaceutical Society of Japan

Keywords

Details 詳細情報について

  • CRID
    1390001206132120832
  • NII Article ID
    130006731096
  • DOI
    10.14894/medchem.26.3_138
  • ISSN
    24328626
    24328618
  • Text Lang
    ja
  • Data Source
    • JaLC
    • CiNii Articles
  • Abstract License Flag
    Disallowed

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