Discovery of DS34942424: An orally potent analgesic without mu opioid receptor agonist activity |
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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, R&D Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan;3. Intellectual Property Department, Global Brand Strategy Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan;1. Key Laboratory of Functional Small Organic Molecules, Ministry of Education, and College of Life Science, Jiangxi Normal University, Nanchang, Jiangxi 330022, China;2. Jiangxi Province’s Key Laboratory of Green Chemistry, and Department of Chemistry, Jiangxi Normal University, Nanchang, Jiangxi, 330022, China;1. School of Pharmacy, Nanjing Medical University, Nanjing 211166, China;2. Centre for Integrated Preclinical Drug Development, The University of Queensland, Brisbane, QLD 4072, Australia;3. Tohoku Pharmaceutical University, 4-1 Komatsushima 4-chome, Aoba-ku, Sendai 981-8558, Japan;4. Medicinal Chemistry Group, Laboratory of Pharmacology and Chemistry, National Institute of Environmental Health Science, Research Triangle Park, NC 27709, USA;5. Collaborative Innovation Center for Cardiovascular Disease Translational Medicine, Nanjing Medical University, Nanjing 211166, China;1. Department of Chemistry and Biochemistry, University of Wisconsin-Milwaukee, Milwaukee, WI 53211, USA;2. Center for Biomolecular Science and Engineering, Naval Research Laboratory, Code 6930, Washington, D.C. 20375, USA;1. Merck & Co. Inc., 2000 Galloping Hill Road, Kenilworth, NJ 07033, USA;2. Scynexis Inc., 1 Evertrust Plaza, Jersey City, NJ 07302, USA |
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| 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. |
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| Keywords: | Conolidine Alkaloid Analgesic Non-opioid analgesics |
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