6-(hexyloxy)-2-naphthonitrile | 61699-18-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 萘
• 英文名称: 6-(hexyloxy)-2-naphthonitrile
• 英文别名: 2-Hexyloxy-6-cyan-naphthalin；6-(Hexyloxy)naphthalene-2-carbonitrile；6-hexoxynaphthalene-2-carbonitrile
• CAS: 61699-18-1
• 化学式: C₁₇H₁₉NO
• 分子量: 253.344
• InChiKey: SXWTXNMYAUWRDZ-UHFFFAOYSA-N

物化性质

• 熔点：
  57-61 °C(Solv: ligroine (8032-32-4))
• 沸点：
  408.2±18.0 °C(Predicted)
• 密度：
  1.06±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  19
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  33
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  6-(hexyloxy)-2-naphthonitrile 在 6-chloro-3-((dimethylamino)(dimethyliminio)methyl)-1H-benzo[d][1,2,3]triazol-3-ium-1-olatehexafluorophosphate(V) 、 盐酸羟胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 tert-butyl (S)-2-(3-(6-(hexyloxy)naphthalen-2-yl)-1,2,4-oxadiazol-5-yl)pyrrolidine-1-carboxylate
  参考文献：
  名称：

  萘基鞘氨醇激酶2抑制剂的结构活性关系研究和分子建模。

  摘要：

  鞘氨醇激酶的两个同工型（SphK1和SphK2）是将鞘氨醇磷酸化为鞘氨醇-1-磷酸（S1P）的唯一酶，鞘氨醇是一种多效脂质介体，参与许多细胞过程，包括迁移，增殖和炎症。SphK是多种疾病的靶标，例如癌症，纤维化以及阿尔茨海默氏病和镰状细胞病。在这里，我们公开了含萘的SphK抑制剂的结构活性图和分子建模研究，这些研究揭示了控制SphK选择性的关键分子开关。

  DOI：

  10.1021/acsmedchemlett.5b00304
• 作为产物：
  描述：

  6-溴-2-萘酚 在 吡啶 、 sodium ethanolate 、 copper(II) sulfate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 6-(hexyloxy)-2-naphthonitrile
  参考文献：
  名称：

  Wagner; Lischke; Markwardt, Pharmazie, 1977, vol. 32, # 12, p. 761 - 763

  摘要：

  DOI：

文献信息

• [EN] SPHINGOSINE KINASE INHIBITORS<br/>[FR] INHIBITEURS DE LA SPHINGOSINE KINASE
  申请人：LYNCH KEVIN

  公开号：WO2016054261A1

  公开（公告）日：2016-04-07

  Sphingosine kinases are enzymes that catalyze the biosynthesis of sphingosine-1-phosphate. The invention provides compounds that are effective for inhibition of sphingosine kinase type 1, sphingosine kinase type 2, or both. Certain compounds are selective for sphingosine kinase type 2 relative to sphingosine kinase type 1. Compounds of the invention can be used in treatment of a range of diseases wherein increasing the level of sphingosine-1-phosphate in blood is medically indicated. Diseases that can be treated by administration of an effective dose of a compound of the invention include a neoplastic disease that involves excess vascular growth; macular degeneration or diabetic retinopathy; an allergic disease such as asthma, an inflammatory disease of the eye such as uveitis, scleritis, or vitritis; an inflammatory disease of the kidney; a fibrotic disease; atherosclerosis; or pulmonary arterial hypertension. A compound of the invention can be used to improve the integrity of a vascular barrier in a disease where the vascular barrier is disrupted, such as cancer or Alzheimer's disease.

  鞘氨醇激酶是催化鞘氨醇-1-磷酸酯生物合成的酶。该发明提供了对鞘氨醇激酶1型、鞘氨醇激酶2型或两者均具有效抑制作用的化合物。某些化合物相对于鞘氨醇激酶1型具有选择性作用于鞘氨醇激酶2型。该发明的化合物可用于治疗一系列疾病，其中增加血液中鞘氨醇-1-磷酸酯水平在医学上是指示的。通过给予该发明的化合物有效剂量可以治疗的疾病包括涉及过度血管生长的肿瘤性疾病；黄斑变性或糖尿病视网膜病变；哮喘等过敏性疾病，眼部炎症性疾病如葡萄膜炎、巩膜炎或玻璃体炎；肾脏炎症性疾病；纤维化疾病；动脉粥样硬化；或肺动脉高压。该发明的化合物可用于改善血管屏障的完整性，在血管屏障受损的疾病中，如癌症或阿尔茨海默病。
• [EN] SPHINGOSINE KINASE INHIBITOR AMIDOXIME PRODRUGS<br/>[FR] PROMÉDICAMENTS D'AMIDOXINE INHIBITEURS DE LA SPHINGOSINE KINASE
  申请人：THORPE STEVEN BRANDON

  公开号：WO2017172989A1

  公开（公告）日：2017-10-05

  Sphingosine kinases are enzymes that catalyze the biosynthesis of sphingosine-1-phosphate. The invention provides prodrugs of compounds that are effective for inhibition of sphingosine kinase type 1, sphingosine kinase type 2, or both, according to formula (I) as described herein. Formula I compounds are useful in the treatment of a range of diseases wherein increasing the level of sphingosine-1-phosphate in blood is medically indicated. The invention also provides pharmaceutical compositions of Formula I compounds.

  鞘氨醇激酶是催化鞘氨醇-1-磷酸酯生物合成的酶。本发明提供了根据本文所述的公式(I)有效抑制鞘氨醇激酶1型、鞘氨醇激酶2型或两者的化合物的前药。公式I化合物在治疗一系列疾病中是有用的，其中在血液中增加鞘氨醇-1-磷酸酯水平在医学上是指示的。本发明还提供了公式I化合物的药物组合物。
• Sphingosine kinase inhibitors
  申请人：University of Virginia Patent Foundation

  公开号：US10100022B2

  公开（公告）日：2018-10-16

  Sphingosine kinases are enzymes that catalyze the biosynthesis of sphingosine-1-phosphate. The invention provides compounds that are effective for inhibition of sphingosine kinase type 1, sphingosine kinase type 2, or both. Certain compounds are selective for sphingosine kinase type 2 relative to sphingosine kinase type 1. Compounds of the invention can be used in treatment of a range of diseases wherein increasing the level of sphingosine-1-phosphate in blood is medically indicated. Diseases that can be treated by administration of an effective dose of a compound of the invention include a neoplastic disease that involves excess vascular growth; macular degeneration or diabetic retinopathy; an allergic disease such as asthma, an inflammatory disease of the eye such as uveitis, scleritis, or vitritis; an inflammatory disease of the kidney; a fibrotic disease; atherosclerosis; or pulmonary arterial hypertension. A compound of the invention can be used to improve the integrity of a vascular barrier in a disease where the vascular barrier is disrupted, such as cancer or Alzheimer's disease.

  鞘氨醇激酶是催化 1-磷酸鞘氨醇生物合成的酶。本发明提供的化合物可有效抑制鞘氨醇激酶 1 型、鞘氨醇激酶 2 型或两者。相对于 1 型鞘氨醇激酶，某些化合物对 2 型鞘氨醇激酶具有选择性。本发明的化合物可用于治疗一系列疾病，在这些疾病中，提高血液中鞘磷脂-1-磷酸的水平具有医学意义。可通过施用有效剂量的本发明化合物治疗的疾病包括：涉及血管过度生长的肿瘤性疾病；黄斑变性或糖尿病视网膜病变；过敏性疾病，如哮喘；眼部炎症性疾病，如葡萄膜炎、巩膜炎或玻璃体炎；肾脏炎症性疾病；纤维化疾病；动脉粥样硬化；或肺动脉高压。本发明的化合物可用于改善血管屏障被破坏的疾病（如癌症或阿尔茨海默病）中血管屏障的完整性。
• Sphingosine kinase inhibitor amidoxime prodrugs
  申请人：University of Virginia Patent Foundation

  公开号：US11180489B2

  公开（公告）日：2021-11-23

  Sphingosine kinases are enzymes that catalyze the biosynthesis of sphingosine-1-phosphate. The invention provides prodrugs of compounds that are effective for inhibition of sphingosine kinase type 1, sphingosine kinase type 2, or both, according to formula (I) as described herein. Formula I compounds are useful in the treatment of a range of diseases wherein increasing the level of sphingosine-1-phosphate in blood is medically indicated. The invention also provides pharmaceutical compositions of Formula I compounds.

  鞘氨醇激酶是催化鞘氨醇-1-磷酸的生物合成的酶。本发明提供了有效抑制鞘氨醇激酶 1 型、鞘氨醇激酶 2 型或二者的化合物原药，如本文所述的式 (I)。式 I 化合物可用于治疗一系列疾病，在这些疾病中，提高血液中鞘磷脂-1-磷酸的水平具有医学指征。本发明还提供了式 I 化合物的药物组合物。
• WAGNER G.; LISCHKE I.; MARKWARDT F.; RICHTER P.; STUERZEBECHER J.; WALSMA+, PHARMAZIE <PHAR-AT>, 1977, 32, NO 12, 761-763
  作者：WAGNER G.、 LISCHKE I.、 MARKWARDT F.、 RICHTER P.、 STUERZEBECHER J.、 WALSMA+

  DOI：——

  日期：——