We have discovered novel benzofuran-based S1P1 agonists with excellent in vitro potency and selectivity. 1-((4-(5-Benzylbenzofuran-2-yl)-3-fluorophenyl)methyl) azetidine-3-carboxylic acid (18) is a potent S1P1 agonist with >1000x selectivity over S1P3. It demonstrated a good in vitro ADME profile and excellent oral bioavailability across species. Dosed orally at 0.3 mg/kg, 18 significantly reduced blood lymphocyte counts 24 h postdose and demonstrated efficacy in a mouse EAE model of relapsing MS.

中文翻译：

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作为有效的口服活性S1P1受体激动剂的苯并呋喃衍生物：MS的临床前铅分子。

我们发现了新型的基于苯并呋喃的S1P1激动剂，具有出色的体外效价和选择性。1-（（4-（5-苄基苯并呋喃-2-基）-3-氟苯基）甲基）氮杂环丁烷-3-羧酸（18）是一种强效的S1P1激动剂，选择性比S1P3高1000倍。它显示出良好的体外ADME谱和跨物种的优异口服生物利用度。口服后以0.3 mg / kg的剂量给药18小时，可显着降低18的血液淋巴细胞计数，并在复发性MS的小鼠EAE模型中证明了疗效。