Agonism of S1P₁ receptor has been proven to be responsible for peripheral blood lymphopenia and elicts the identification of various S1P₁ modulators. In this paper we described a series of oxadiazole-based S1P₁ direct-acting agonists disubstituted on terminal benzene ring, with high potency for S1P₁ receptor and favorable selectivity against S1P₃ receptor. In addition, two representative agents named 16-3b and 16-3g demonstrated impressive efficacy in lymphocyte reduction along with reduced effect on heart rate when orally administered. Furthermore, these compounds have been shown to possess desired pharmacokinetic (PK) and physicochemical profiles. The binding mode between 16-3b and the activated S1P₁ model was also studied.

S1P ₁受体的激动作用已被证明是导致外周血淋巴细胞减少的原因，并引发了各种S1P ₁调节剂的鉴定。在本文中，我们描述了一系列在末端苯环上双取代的基于恶二唑的S1P ₁直接作用激动剂，对S1P ₁受体具有很高的效力，并且对S1P ₃受体具有良好的选择性。此外，两个具有代表性的药物称为16-3B和16 - 3克口服给药后显示出令人印象深刻的减少淋巴细胞功效以及对心率的降低作用。此外，已显示这些化合物具有所需的药代动力学（PK）和理化特性。之间的结合模式16 -图3b和被激活的S1P ₁模型进行了研究。