Merck Serono SA, 9 Chem. des Mines, 1202 Geneva, Switzerland.
Bioorg Med Chem Lett. 2010 Mar 1;20(5):1516-9. doi: 10.1016/j.bmcl.2010.01.102. Epub 2010 Jan 25.
The discovery of a novel series of S1P1 agonists is described. Starting from a micromolar HTS positive, iterative optimization gave rise to several single-digit nanomolar S1P1 agonists. The compounds were able to induce internalization of the S1P1 receptor, and a selected compound was shown to be able to induce lymphopenia in mice after oral dosing.
本文描述了一种新型 S1P1 激动剂系列的发现。从毫摩尔的高通量筛选阳性开始，经过反复优化，得到了几个单位数纳摩尔的 S1P1 激动剂。这些化合物能够诱导 S1P1 受体内化，并且选定的化合物在口服给药后能够在小鼠中诱导淋巴细胞减少。
