Discovery of a novel bicyclic compound,DS54360155, as an orally potent analgesic without mu-opioid receptor agonist activity |
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| Authors: | Tsuyoshi Arita Masayoshi Asano Kazufumi Kubota Yuki Domon Nobuo Machinaga Kousei Shimada |
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| Affiliation: | 1. Medicinal Chemistry Research Laboratories, R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan;2. Specialty Medicine Research Laboratories I, R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan |
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| Abstract: | We synthesized derivatives of a natural alkaloid, conolidine, and evaluated these derivatives in the acetic acid-induced writhing test and formalin test in ddY mice after oral administration. As a result, we identified (5S)-6-methyl-1,3,4,5,6,8-hexahydro-7H-2,5-methano[1,5]diazonino[7,8-b]indol-7-one sulfate salt, 15a (DS54360155), with a unique and original bicyclic skeleton, as an analgesic more potent than conolidine. Moreover, 15a did not exhibit mu-opioid receptor agonist activity. |
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| Keywords: | Corresponding author. Conolidine Indole alkaloid Analgesic Acetic acid writhing test Non-opioid analgesic |
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