(S)-FTY720 Vinylphosphonate | 1142015-13-1

• 分子结构分类: 有机化合物 - 有机氮化合物
• 英文名称: (S)-FTY720 Vinylphosphonate
• 英文别名: (S)-FTY720-ene-phosphonate；(3S)-3-amino-3-(hydroxymethyl)-5-(4'-octylphenyl)-pent-(1E)-enylphosphonic acid；(S)-Fingolimod Vinylphosphonate；[(E,3S)-3-amino-3-(hydroxymethyl)-5-(4-octylphenyl)pent-1-enyl]phosphonic acid
• CAS: 1142015-13-1
• 化学式: C₂₀H₃₄NO₄P
• 分子量: 383.468
• InChiKey: YWQUROWPKWKDNA-APHAIJBRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  26
• 可旋转键数：
  13
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  104
• 氢给体数：
  4
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-FTY720 Vinylphosphonate 在 10% Pd(OH)2 on carbon 、 氢气 作用下， 以 甲醇 为溶剂， 以91%的产率得到(S)-FTY-phosphonate
  参考文献：
  名称：

  免疫抑制剂 FTY720 的手性乙烯基膦酸酯和膦酸酯类似物

  摘要：

  描述了 FTY720 的手性等排膦酸酯类似物的第一个对映选择性合成。其中一个类似物 FTY720-( E )-乙烯基膦酸酯 ( S )- 5，而不是它的R对映异构体，在肠上皮细胞中引起有效的抗凋亡作用，表明它通过受体的对映选择性激活发挥作用。( S ) -5未能激活 1-磷酸鞘氨醇 1 型 (S1P 1 ) 受体。

  DOI：

  10.1021/jo900023u
• 作为产物：
  描述：

  4-正辛基苯乙烯 在 titanium(IV) isopropylate 、 盐酸 、 sodium azide 、 三甲基溴硅烷 、 水 、 potassium carbonate 、 D-(-)-酒石酸二异丙酯 、 氯化铵 、 tin(ll) chloride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 异丙醇 为溶剂， 反应 9.0h， 生成 (S)-FTY720 Vinylphosphonate
  参考文献：
  名称：

  (S)-FTY720 乙烯基膦酸酯类似物的合成及其作为鞘氨醇激酶 1 抑制剂和激活剂的潜力评估

  摘要：

  鞘氨醇激酶 1 (SK1) 在许多癌症中过度表达，为这些细胞提供选择性生长和存活优势。因此，SK1 是可以促进癌细胞凋亡的抗癌剂的靶标。在之前的工作中，我们合成了一种新型的变构 SK1 抑制剂，( S )-FTY720 乙烯基膦酸酯。我们现在报告了一种更快速的抑制剂途径，该途径以 B-烷基 Suzuki 偶联为关键步骤，并表明用叠氮基取代 (S)-FTY720 乙烯基膦酸酯中的氨基可将乙烯基膦酸酯从变构抑制剂转化为活化剂SK1 在低微摩尔浓度。我们的结果证明了使用（S)-FTY720 乙烯基膦酸酯支架来定义 SK1 变构位点的结构-活性关系。

  DOI：

  10.1016/j.bmc.2013.02.042

文献信息

• Method Of Treating Acute Lung Injury Using Sphingosine 1 Phosphate Analogs Or Sphingosine 1 Phosphate Receptor Agonists
  申请人：Garcia Joe G.N.

  公开号：US20130079309A1

  公开（公告）日：2013-03-28

  The invention provides methods for treating or reducing the risk of developing acute lung injury manifested by increased vascular permeability. Also provided are pharmaceutical compositions comprising an FTY720 analog or derivative and/or SEW 2871 for use in the disclosed methods. The invention also provides methods for treating or reducing the risk of developing acute lung injury resulting from dysregulation of ceramide/sphingolipid pathway, more specifically, acute lung injury resulting from radiation.

  本发明提供了治疗或减少因增加血管通透性而表现为急性肺损伤的方法。还提供了包含FTY720类似物或衍生物和/或SEW 2871的药物组合物，用于所述方法。本发明还提供了治疗或减少因鞘氨醇/鞘脂代谢通路失调而导致的急性肺损伤的方法，更具体地说，是由放射线引起的急性肺损伤。
• Stabilization of alcohol intoxication-induced cardiovascular instability
  申请人：Breslin Jerome William

  公开号：US10111841B2

  公开（公告）日：2018-10-30

  The present invention concerns use of an agent that increases sphingosine-1-phosphate (S1P) receptor activity, such as S1P, or an S1P receptor agonist, for treatment of alcohol-intoxicated subjects will help stabilize blood pressure and improve resuscitation efforts in alcohol-intoxicated subjects, including alcohol-intoxicated trauma patients. Another aspect concerns a kit for stabilization of alcohol-intoxicated subjects, comprising an agent that increases S1P receptor activity.

  本发明涉及一种增加鞘氨醇-1-磷酸（S1P）受体活性的药剂，如 S1P 或 S1P 受体激动剂，用于治疗酒精中毒者，将有助于稳定血压和改善酒精中毒者（包括酒精中毒的创伤患者）的复苏工作。另一个方面涉及一种用于稳定酒精中毒受试者的试剂盒，其中包含一种能提高 S1P 受体活性的制剂。
• COMBINED CHEMICAL MODIFICATION OF SPHINGOSINE-1-PHOSPHATE (S1P) AND CXCR4 SIGNALLING PATHWAYS FOR HEMATOPOIETIC STEM CELL (HSC) MOBILIZATION AND ENGRAFTMENT
  申请人：CHILDREN'S MEDICAL CENTER CORPORATION

  公开号：US20140193376A1

  公开（公告）日：2014-07-10

  The present embodiments provide for combinations of modulators that increase hematopoietic stem cell engraftment or increase mobilization in vivo. Methods and compositions for modulating the mobilization of stem cells, particularly for promoting or increasing the mobilization of hematopoietic stem cells (HSCs) from the bone marrow to the peripheral blood are disclosed. One aspect of the invention relates to the use of a CXCR4 antagonist that act in concert with specific molar ratios of S1P receptor 1 (S1PR1) modulator agents to promote HSC mobilization. The invention also relates to methods of using these combinations of CXCR4 antagonists and S1PR1 modulator agents for enhancing the mobilization of hematopoietic stem cells when harvesting of the stem cells, for example for the treatment of diseases, disabilities or conditions whereby transplantation of such cells would be beneficial in ameliorating a symptom associated with such diseases, disabilities or conditions. Another aspect of the invention relates to the use of a CXCR4 antagonist that act in concert with different, but specific molar ratios of S1P receptor 1 (S1PR1) modulator agents to promote HSC engraftment and methods for promoting HSC engraftment in a subject in need thereof, e.g., a recipient subject of a bone marrow or HSC transplant. Methods of screening for novel agents and pharmaceutical compositions comprising these agents are also disclosed.
• STABILIZATION OF ALCOHOL INTOXICATION-INDUCED CARDIOVASCULAR INSTABILITY
  申请人：BRESLIN JEROME WILLIAM

  公开号：US20170020826A1

  公开（公告）日：2017-01-26

  The present invention concerns use of an agent that increases sphingosine-1-phosphate (S1P) receptor activity, such as S1P, or an S1P receptor agonist, for treatment of alcohol-intoxicated subjects will help stabilize blood pressure and improve resuscitation efforts in alcohol-intoxicated subjects, including alcohol-intoxicated trauma patients. Another aspect concerns a kit for stabilization of alcohol-intoxicated subjects, comprising an agent that increases S1P receptor activity.
• US9763980B2
  申请人：——

  公开号：US9763980B2

  公开（公告）日：2017-09-19