Tetrahydropyridine derivatives with inhibitory activity on the production of proinflammatory cytokines: Part 2 |
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| Authors: | Akira Nakao Nobuyuki Ohkawa Takayoshi Nagasaki Takashi Kagari Hiromi Doi Takaichi Shimozato Shigeru Ushiyama Kazumasa Aoki |
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| Institution: | 1. Medicinal Chemistry Research Laboratories II, Daiichi Sankyo Co., Ltd, 1-16-13 Kitakasai, Edogawa-ku, Tokyo134-8630, Japan;2. Medicinal Chemistry Research Laboratories I, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo140-8710, Japan;3. Research Department II, Daiichi Sankyo RD Associe Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan;4. Biological Research Laboratories III, Daiichi Sankyo Co., Ltd, 1-16-13 Kitakasai, Edogawa-ku, Tokyo 134-8630, Japan;5. R&D Planning Department, Daiichi Sankyo Co., Ltd, 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan |
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| Abstract: | We previously reported a novel pyrrole derivative 1 which possesses a tetrahydropyridine group at the β-position with a proinflammatory cytokine TNFα production inhibitor. Herein, we report the synthesis and biological activity of N- and α-position substituted tetrahydropyridine derivatives. In this series, we found that compound 3o showed good inhibitory activity in vitro (inhibition of lipopolysaccharide (LPS)-induced TNFα production in human whole blood, IC50 = 0.44 μM) and compound 3i demonstrated potent inhibitory activity in vivo (inhibition of LPS-induced TNFα production in mice, ID50 = 1.42 mg/kg). |
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