Identification of benzoxazole analogs as novel, S1P₃ sparing S1P₁ agonists

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• 作者：Guanghui Deng ; Qinghua Meng ; Qian Liu ; Xuesong Xu ; Qiongfeng Xu ; Feng Ren ; Taylor B. Guo ; Hongtao Lu ; Jia-Ning Xiang ; John D. Elliott ; Xichen Lin ; ^{xichen.2.lin@gsk.com}
• 关键词：Sphingosine-1-phosphate (S1P) ; Agonist ; Lymphopenia ; Multiple sclerosis
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 期刊代码：10_0960894x
• 类别：ch
• 出版时间：15 June, 2012
• 卷：22
• 期：12
• 页码：3973-3977
• 文件大小：2479 K

摘要

A novel series of benzoxazole-derived S1P₁ agonists were designed based on scaffold hopping molecular design strategy combined with computational approaches. Extensive SAR studies led to the discovery of compound 17d as a selective S1P₁ agonist (over S1P₃) with high CNS penetration and favorable DMPK properties. 17d also demonstrated in vivo pharmacological efficacy to reduce blood lymphocyte in mice after oral administration.