Discovery of CS-2100, a potent, orally active and S1P 3-sparing S1P 1 agonist

T Nakamura, M Asano, Y Sekiguchi, Y Mizuno…

文献索引：Nakamura, Tsuyoshi; Asano, Masayoshi; Sekiguchi, Yukiko; Mizuno, Yumiko; Tamaki, Kazuhiko; Kimura, Takako; Nara, Futoshi; Kawase, Yumi; Shimozato, Takaichi; Doi, Hiromi; Kagari, Takashi; Tomisato, Wataru; Inoue, Ryotaku; Nagasaki, Miyuki; Yuita, Hiroshi; Oguchi-Oshima, Keiko; Kaneko, Reina; Watanabe, Nobuaki; Abe, Yasuyuki; Nishi, Takahide Bioorganic and Medicinal Chemistry Letters, 2012 , vol. 22, # 4 p. 1788 - 1792

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被引用次数: 13

摘要

S1P3-sparing S1P1 agonists have attracted attention as a suppressant of autoimmunity with reduced side effects. Our synthetic efforts and extensive SAR studies led to the discovery of 10b named CS-2100 with the EC50 value of 4.0 nM for human S1P1 and over 5000-fold selectivity against S1P3. The in vivo immunosuppressive efficacy was evaluated in rats on host versus graft reaction and the ID50 value was determined at 0.407 mg/kg. The docking ...