Discovery of DS34942424: An orally potent analgesic without mu opioid receptor agonist activity

  • Bioorg Med Chem. 2020 Nov 1;28(21):115714. doi: 10.1016/j.bmc.2020.115714.
Tsuyoshi Arita  1 ,  Masayoshi Asano  2 ,  Kazufumi Kubota  3 ,  Yuki Domon  3 ,  Nobuo Machinaga  4 ,  Kousei Shimada  4
Affiliations
  • 1. Medicinal Chemistry Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: [email protected].
  • 2. Intellectual Property Department, Global Brand Strategy Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • 3. Specialty Medicine Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
  • 4. Medicinal Chemistry Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
PMID: 33065431 DOI: 10.1016/j.bmc.2020.115714
Abstract

We identified (5'S)-10'-fluoro-6'-methyl-5',6'-dihydro-3'H-spiro[cyclopropane-1,4'-[2,6]diaza[2,5]methano[2,6]benzodiazonin]-7'(1'H)-one, 22b (DS34942424) with a unique and original bicyclic skeleton. 22b showed an orally potent analgesic in the acetic acid-induced writhing test and formalin test in ddY mice without sedation. Moreover, 22b did not exhibit mu Opioid Receptor agonist activity.

Keywords
Alkaloid; Analgesic; Conolidine; Non-opioid analgesics.
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