Discovery of CS-0777: a potent, selective, and orally active S1P1 agonist

T Nishi, S Miyazaki, T Takemoto, K Suzuki…

Index: Nishi, Takahide; Miyazaki, Shojiro; Takemoto, Toshiyasu; Suzuki, Keisuke; Iio, Yukiko; Nakajima, Katsuyoshi; Ohnuki, Takashi; Kawase, Yumi; Nara, Futoshi; Inaba, Shinichi; Izumi, Takashi; Yuita, Hiroshi; Oshima, Keiko; Doi, Hiromi; Inoue, Ryotaku; Tomisato, Wataru; Kagari, Takashi; Shimozato, Takaichi ACS Medicinal Chemistry Letters, 2011 ,  vol. 2,  # 5  p. 368 - 372

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Citation Number: 32

Abstract

CS-0777 (3) is phosphorylated in vivo, and the phosphate of CS-0777 (CS-0777-P)(4) acts as a selective S1P receptor-1 (S1P1) modulator. We report herein the synthesis of CS-0777 and CS-0777-P, pharmacological effects such as S1P1 and S1P3 agonist activity in vitro, peripheral blood lymphocyte lowering effects and the suppressive effect on experimental autoimmune encephalomyelitis (EAE), and also the pharmacokinetics in rats. CS-0777-P ...