1-(4-(5-(5-isobutyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)-benzyl)azetidine-3-carboxylic acid, trifluoroacetic acid salt | 1236188-68-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(4-(5-(5-isobutyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)-benzyl)azetidine-3-carboxylic acid, trifluoroacetic acid salt
• 英文别名: 1-(4-(5-(5-isobutyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)benzyl)azetidine-3-carboxylic acid 2,2,2-trifluoroacetate
• CAS: 1236188-68-3
• 化学式: C₂HF₃O₂*C₂₃H₂₈N₄O₄
• 分子量: 538.524
• InChiKey: FKIAKJMAKWHEDI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.69
• 重原子数：
  38.0
• 可旋转键数：
  9.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  142.79
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为产物：
  描述：

  tert-butyl 1-(4-(5-(5-isobutyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)-benzyl)azetidine-3-carboxylate 、 三氟乙酸 反应 2.5h， 以92%的产率得到1-(4-(5-(5-isobutyl-4-propylisoxazol-3-yl)-1,2,4-oxadiazol-3-yl)-benzyl)azetidine-3-carboxylic acid, trifluoroacetic acid salt
  参考文献：
  名称：

  [EN] SUBSTITUTED OXADIAZOLE DERIVATIVES AS S1P AGONISTS IN THE TREATMENT OF AUTOIMMUNE AND INFLAMMATORY DISEASES
  [FR] DÉRIVÉS D'OXADIAZOLE SUBSTITUÉS COMME AGONISTES DE S1P DANS LE TRAITEMENT DE MALADIES AUTO-IMMUNES ET INFLAMMATOIRES

  摘要：

  揭示了化合物的结构式 (I) [在此插入化学结构] (I) 或其药学上可接受的盐，其中 Q 是 [在此插入化学结构] 或 [在此插入化学结构]；R1 是烷基或芳基，所述芳基可选择性地取代一个至五个取代基，独立选择自 C1 至 C6 烷基、C1 至 C4 卤代烷基、OR4 和/或卤素；而 R2、R3、R4 和 n 在此有定义。还揭示了将这些化合物用作 G 蛋白偶联受体 S1P1 的选择性激动剂的方法，以及包含这些化合物的药物组合物。这些化合物在治疗、预防或减缓多种治疗领域的疾病或疾病进展方面具有用途，如自身免疫疾病和血管疾病。

  公开号：

  WO2010085581A1

文献信息

• Potent and Selective Agonists of Sphingosine 1-Phosphate 1 (S1P₁): Discovery and SAR of a Novel Isoxazole Based Series
  作者：Scott H. Watterson、Junqing Guo、Steve H. Spergel、Charles M. Langevine、Robert V. Moquin、Ding Ren Shen、Melissa Yarde、Mary Ellen Cvijic、Dana Banas、Richard Liu、Suzanne J. Suchard、Kathleen Gillooly、Tracy Taylor、Sandra Rex-Rabe、David J. Shuster、Kim W. McIntyre、Georgia Cornelius、Celia D’Arienzo、Anthony Marino、Praveen Balimane、Bethanne Warrack、Luisa Salter-Cid、Murray McKinnon、Joel C. Barrish、Percy H. Carter、William J. Pitts、Jenny Xie、Alaric J. Dyckman

  DOI：10.1021/acs.jmedchem.6b00089

  日期：2016.3.24

  Sphingosine 1-phosphate (S1P) is the endogenous ligand for the sphingosine 1-phosphate receptors (S1P(1-5)) and evokes a variety of cellular responses through their stimulation. The interaction of S1P with the S1P receptors plays a fundamental physiological role in a number of processes including vascular development and stabilization, lymphocyte migration, and proliferation. Agonism of S1P(1), in particular, has been shown to play a significant role in lymphocyte trafficking from the thymus and secondary lymphoid organs, resulting in immunosuppression. This article will detail the discovery and SAR of a potent and selective series of isoxazole based full agonists of S1P(1). Isoxazole 6d demonstrated impressive efficacy when administered orally in a rat model of arthritis and in a mouse experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis.