Fused tricyclic indoles as S1P1 agonists with robust efficacy in animal models of autoimmune disease
Fused tricyclic indoles as S1P1 agonists with robust efficacy in animal models of autoimmune disease
复制标题
DOI：
10.1016/j.bmcl.2012.04.129
复制
发表时间：
2012-07-01
影响因子：
2.7
通讯作者：
Jones, Robert M.
中科院分区：
文献类型：
--
作者：
Buzard, Daniel J.;Han, Sangdon;Jones, Robert M.
两个系列的稠合三环吲哚被鉴定为有效和选择性的S1P(1)激动剂。在体内，这些激动剂使循环中的淋巴细胞显着减少，这在几种自身免疫性疾病的啮齿动物模型中转化为强大的疗效。重要的是，这些激动剂在体外没有S1P(3)受体的任何活性，相应地也不会在远程治疗的大鼠中产生S1P(3)介导的心动过缓。(C)2012爱思唯尔有限公司。保留所有权利。
Two series of fused tricyclic indoles were identified as potent and selective S1P(1) agonists. In vivo these agonists produced a significant reduction in circulating lymphocytes which translated into robust efficacy in several rodent models of autoimmune disease. Importantly, these agonists were devoid of any activity at the S1P(3) receptor in vitro, and correspondingly did not produce S1P(3) mediated bradycardia in telemeterized rat. (C) 2012 Elsevier Ltd. All rights reserved.