Discovery of conolidine derivative DS39201083 as a potent novel analgesic without mu opioid agonist activity

  • Bioorg Med Chem Lett. 2019 Aug 1;29(15):1938-1942. doi: 10.1016/j.bmcl.2019.05.045.
Tsuyoshi Arita  1 ,  Masayoshi Asano  2 ,  Kazufumi Kubota  2 ,  Yuki Domon  2 ,  Nobuo Machinaga  2 ,  Kousei Shimada  2
Affiliations
  • 1. R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. Electronic address: [email protected].
  • 2. R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan.
PMID: 31147104 DOI: 10.1016/j.bmcl.2019.05.045
Abstract

We discovered a novel compound, 5-methyl-1,4,5,7-tetrahydro-2,5-ethanoazocino[4,3-b]indol-6(3H)-one sulfuric acid salt (DS39201083), which was formed by derivatization of a natural product, conolidine. DS39201083 had a unique bicyclic skeleton and was a more potent analgesic than conolidine, as revealed in the acetic acid-induced writhing test and formalin test in ddY mice. The compound showed no agonist activity at the mu Opioid Receptor.

Keywords
Acetic acid writhing test; Analgesic; Conolidine; Indole alkaloid; Non-opioid.
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