1,1-dimethylethyl 2-[5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydro-1-isoquinolinyl]acetate | 1165938-46-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1,1-dimethylethyl 2-[5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydro-1-isoquinolinyl]acetate
• 英文别名: 1,1-dimethylethyl (5-(5-(3-chloro-4-(1-methylethyloxy)phenyl)-1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydro-1-isoquinolinyl)acetate；Tert-butyl 2-[5-[5-(3-chloro-4-propan-2-yloxyphenyl)-1,2,4-oxadiazol-3-yl]-1,2,3,4-tetrahydroisoquinolin-1-yl]acetate
• CAS: 1165938-46-4
• 化学式: C₂₆H₃₀ClN₃O₄
• 分子量: 483.995
• InChiKey: OGXQOXLINBAUII-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  86.5
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1,1-dimethylethyl 2-[5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydro-1-isoquinolinyl]acetate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 18.0h， 以92%的产率得到[5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydro-1-isoquinolinyl]acetic acid hydrochloride
  参考文献：
  名称：

  [EN] OXADIAZOLE DERIVATIVES ACTIVE ON SPHINGOSINE-1-PHOSPHATE (SIP)
  [FR] DÉRIVÉS D'OXADIAZOLE ACTIFS SUR LA SPHINGOSINE-1-PHOSPHATE (S1P)

  摘要：

  本申请披露了一种基于噁二唑的化合物，其化学式为（I），活性为鞘氨醇-1-磷酸（S1P），特别适用于治疗红斑狼疮。其中，A为苯基或5或6元杂环芳基环；B从以下式中选取：(a)、(b)、(c)。

  公开号：

  WO2009080728A1
• 作为产物：
  描述：

  3-氯-4-羟基苯甲酸甲酯 在 盐酸 、 N-溴代丁二酰亚胺(NBS) 、 sodium hydride 、 potassium carbonate 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 36.25h， 生成 1,1-dimethylethyl 2-[5-(5-{3-chloro-4-[(1-methylethyl)oxy]phenyl}-1,2,4-oxadiazol-3-yl)-1,2,3,4-tetrahydro-1-isoquinolinyl]acetate
  参考文献：
  名称：

  Optimization of Sphingosine-1-phosphate-1 Receptor Agonists: Effects of Acidic, Basic, and Zwitterionic Chemotypes on Pharmacokinetic and Pharmacodynamic Profiles

  摘要：

  The efficacy of the recently approved drug fingolimod (FTY720) in multiple sclerosis patients results from the action of its phosphate metabolite on sphingosine-1-phosphate S1P(1) receptors, while a variety of side effects have been ascribed to its S1P(3) receptor activity. Although S1P and phospho-fingolimod share the same structural elements of a zwitterionic headgroup and lipophilic tail, a variety of chemotypes have been found to show S1P(1) receptor agonism. Here we describe a study of the tolerance of the S1P(1) and S1P(3) receptors toward bicyclic heterocycles of systematically varied shape and connectivity incorporating acidic, basic, or zwitterionic headgroups. We compare their physicochemical properties, their performance in in vitro and in vivo pharmacokinetic models, and their efficacy in peripheral lymphocyte lowering. The campaign resulted in the identification of several potent S1P(1) receptor agonists with good selectivity vs S1P(3) receptors, efficacy at <1 mg/kg oral doses, and developability properties suitable for progression into preclinical development.

  DOI：

  10.1021/jm5010336

文献信息

• OXADIAZOLE DERIVATIVES ACTIVE ON SPHINGOSINE-1-PHOSPHATE (SIP)
  申请人：Heer Jag Paul

  公开号：US20100298373A1

  公开（公告）日：2010-11-25

  The present invention relates to novel oxadiazole derivatives having pharmacological activity, processes for their preparation, pharmaceutical compositions containing them and their use in the treatment of various disorders.

  本发明涉及具有药理活性的新型噁唑烷衍生物，其制备方法，包含它们的制药组合物以及它们在治疗各种疾病方面的应用。
• US8263620B2
  申请人：——

  公开号：US8263620B2

  公开（公告）日：2012-09-11