129623-62-7Relevant articles and documents
Discovery of CS-2100, a potent, orally active and S1P3-sparing S1P1 agonist
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
scheme or table, p. 1788 - 1792 (2012/04/04)
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 ID 50 value was determined at 0.407 mg/kg. The docking studies of CS-2100 with the homology model of S1P1 and S1P3 showed that the ethyl group on the thiophene ring of CS-2100 was sterically hindered by Phe263 in S1P3, not in the case of Leu276 in S1P1. This observation gives an explanation for the excellent S1P3-sparing characteristic of CS-2100.
