2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1H-3-benzazepin-6-yl)-1,2,4-oxadiazol-5-yl]benzonitrile hydrochloride | 1167415-50-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯氮卓类
• 英文名称: 2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1H-3-benzazepin-6-yl)-1,2,4-oxadiazol-5-yl]benzonitrile hydrochloride
• 英文别名: 2-propan-2-yloxy-5-[3-(2,3,4,5-tetrahydro-1H-3-benzazepin-6-yl)-1,2,4-oxadiazol-5-yl]benzonitrile;hydrochloride
• CAS: 1167415-50-0
• 化学式: C₂₂H₂₂N₄O₂*ClH
• 分子量: 410.903
• InChiKey: SIRZDDXJWHZOMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.17
• 重原子数：
  29
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  84
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1,1-dimethylethyl 6-(5-{3-cyano-4-[(1-methylethyl)oxy] phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate 在 三氟乙酸 、 sodium hydroxide 、 盐酸 作用下， 以 二氯甲烷 、 水 、 1,4-二氧六环 为溶剂， 反应 1.0h， 以100%的产率得到2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1H-3-benzazepin-6-yl)-1,2,4-oxadiazol-5-yl]benzonitrile 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），对神经酰胺-1-磷脂酸（S1P）具有活性，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；R1为最多两个取代基，可独立选择自卤素、C（1-3）烷氧基、C（1-3）氟烷基、氰基、可选择取代的苯基、C（1-3）氟烷氧基、C（1-6）烷基和C（3-6）环烷基；R2为氢、卤素或C（1-4）烷基；B为以下选项中的7元饱和环之一：（a）（b）（c）；R3为氢或（CH2）1-4MCO2H；R4为氢或C（1-3）烷基，可由氧原子中断。

  公开号：

  WO2009080725A1
• 作为试剂：
  描述：

  1,1-dimethylethyl 6-(5-{3-cyano-4-[(1-methylethyl)oxy] phenyl}-1,2,4-oxadiazol-3-yl)-1,2,4,5-tetrahydro-3H-3-benzazepine-3-carboxylate 、 三氟乙酸 、 二氯甲烷 在 二氯甲烷 、 sodium hydroxide 、 盐酸 、 1,4-二氧六环 、 2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1H-3-benzazepin-6-yl)-1,2,4-oxadiazol-5-yl]benzonitrile hydrochloride 作用下， 反应 1.0h， 以to give the HCl salt, 2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1H-3-benzazepin-6-yl)-1,2,4-oxadiazol-5-yl]benzonitrile hydrochloride (438 mg, 1.066 mmol, 100% yield) as an off-white powder的产率得到2-[(1-methylethyl)oxy]-5-[3-(2,3,4,5-tetrahydro-1H-3-benzazepin-6-yl)-1,2,4-oxadiazol-5-yl]benzonitrile hydrochloride
  参考文献：
  名称：

  OXADIAZOLE DERIVATIVES ACTIVE ON SPHINGOSINE-1-PHOSPHATE (SIP)

  摘要：

  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、含有它们的制药组合物以及它们在治疗各种疾病中的用途。

  公开号：

  US20100273771A1

文献信息

• COMPOUNDS
  申请人：HEER Jag Paul

  公开号：US20100174065A1

  公开（公告）日：2010-07-08

  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二唑衍生物，其制备方法，含有它们的药物组合物以及它们在治疗各种疾病中的用途。
• Oxadiazole derivatives active on sphingosine-1-phosphate (S1P)
  申请人：Glaxo Group Limited

  公开号：US08222245B2

  公开（公告）日：2012-07-17

  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二唑衍生物，其制备过程，含有它们的制药组合物以及它们在治疗各种疾病中的应用。
• Optimization of Sphingosine-1-phosphate-1 Receptor Agonists: Effects of Acidic, Basic, and Zwitterionic Chemotypes on Pharmacokinetic and Pharmacodynamic Profiles
  作者：John Skidmore、Jag Heer、Christopher N. Johnson、David Norton、Sally Redshaw、Jennifer Sweeting、David Hurst、Andrew Cridland、David Vesey、Ian Wall、Mahmood Ahmed、Dean Rivers、James Myatt、Gerard Giblin、Karen Philpott、Umesh Kumar、Alexander Stevens、Rino A. Bit、Andrea Haynes、Simon Taylor、Robert Watson、Jason Witherington、Emmanuel Demont、Tom D. Heightman

  DOI：10.1021/jm5010336

  日期：2014.12.26

  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.
• US8222245B2
  申请人：——

  公开号：US8222245B2

  公开（公告）日：2012-07-17