1-(4-(octyloxy)-3-(trifluoromethyl)phenyl)ethanone | 911412-22-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1-(4-(octyloxy)-3-(trifluoromethyl)phenyl)ethanone
• 英文别名: 1-[4-octoxy-3-(trifluoromethyl)phenyl]ethanone
• CAS: 911412-22-1
• 化学式: C₁₇H₂₃F₃O₂
• 分子量: 316.364
• InChiKey: AQDLPUMKLKAJSQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.9
• 重原子数：
  22
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-(4-(octyloxy)-3-(trifluoromethyl)phenyl)ethanone 在 盐酸 、 sodium azide 、 palladium 10% on activated carbon 、 氢气 、 copper(ll) bromide 作用下， 以 甲醇 、 氯仿 、 水 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 2-amino-1-(4-(octyloxy)-3-(trifluoromethyl)phenyl)ethanone hydrochloride
  参考文献：
  名称：

  Discovery of Clinical Candidate GSK1842799 As a Selective S1P₁ Receptor Agonist (Prodrug) for Multiple Sclerosis

  摘要：

  To develop effective oral treatment for multiple sclerosis (MS), we discovered a series of alkyl-substituted biaryl amino alcohols as selective S1P(1) modulators. One exemplar is (S)-2-amino-2-(5-(4-(octyloxy)-3-(trifluoromethyl)phenyl) -1,3,4-thiadiazol-2-yl)propan-1-ol (10, GSK1842799). Upon phosphorylation, the compound (10-P) showed subnanomole S1P(1) agonist activity with >1000x selectivity over S1P(3). The alcohol 10 demonstrated good oral bioavailability and rapid in vivo conversion to 10-P. Dosed orally at 0.1 mg/kg, 10 significantly reduced blood lymphocyte counts 6 h postdose, and at 3 mg/kg, 10 achieved efficacy equivalent to FTY720 in the mouse EAE model of MS. Further pharmacokinetic/pharmacodynamic (PK/PD) study with cynomolgus monkeys indicated that, after oral dosing of 10 at 3.8 mg/kg, the active phosphate reached plasma levels that are comparable to FTY-720 phosphate (FTY-P) revealed in human clinical pharmacokinetics studies. On the basis of the favorable in vitro ADME and in vivo PK/PD properties as well as broad toxicology evaluations, compound 10 (GSK1842799) was selected as a candidate for further clinical development.

  DOI：

  10.1021/ml400194r
• 作为产物：
  描述：

  4'-氟-3'-(三氟甲基)苯乙酮 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 3.17h， 以60%的产率得到1-(4-(octyloxy)-3-(trifluoromethyl)phenyl)ethanone
  参考文献：
  名称：

  WO2008/16692

  摘要：

  公开号：

文献信息

• Methods and compositions for modulating sphingosine-1-phosphate (S1P) receptor activity
  申请人：Evindar Ghotas

  公开号：US20060223866A1

  公开（公告）日：2006-10-05

  The present invention relates to compounds which modulate the activity of the S1P1 receptor, the use of these compounds for treating conditions associated with signaling through the S1P1 receptor, and pharmaceutical compositions comprising these compounds.

  本发明涉及调节S1P1受体活性的化合物，使用这些化合物治疗与S1P1受体信号传导相关的疾病，并包括这些化合物的制药组合物。
• CHEMICAL COMPOUNDS
  申请人：Evindar Ghotas

  公开号：US20100009936A1

  公开（公告）日：2010-01-14

  The invention provides compounds formula I, their preparation, and their use as pharmaceutically active immuno-suppressive agents for the treatment of autoimmune disorders, organ transplant rejection, disorders associated with an activated immune system, as well as other disorders modulated by lymphopenia or SIP receptors.

  该发明提供了化合物I的公式，其制备方法，以及它们作为药物活性的免疫抑制剂用于治疗自身免疫性疾病，器官移植排斥，与激活的免疫系统相关的疾病，以及其他淋巴减少或SIP受体调节的疾病。
• Chemical compounds
  申请人：Evindar Ghotas

  公开号：US20080096938A1

  公开（公告）日：2008-04-24

  The invention provides compounds formula I, their preparation, and their use as pharmaceutically active immunosuppressive agents for the treatment of autoimmune disorders, organ transplant rejection, disorders associated with an activated immune system, as well as other disorders modulated by lymphopenia or S1P receptors.

  本发明提供了化合物I的公式、其制备方法以及其作为药物活性的免疫抑制剂，用于治疗自身免疫性疾病、器官移植排斥、与激活的免疫系统相关的疾病，以及其他受淋巴细胞减少或S1P受体调节的疾病。
• Sphingosine-1-phosphate (SIP) receptor agonists
  申请人：Praecis Pharmaceuticals

  公开号：US07759370B2

  公开（公告）日：2010-07-20

  The invention provides compounds formula I, their preparation, and their use as pharmaceutically active immunosuppressive agents for the treatment of autoimmune disorders, organ transplant rejection, disorders associated with an activated immune system, as well as other disorders modulated by lymphopenia or S1P receptors.

  本发明提供了化合物I的配方、其制备方法以及其作为药理活性免疫抑制剂的用途，用于治疗自身免疫性疾病、器官移植排斥、与激活免疫系统相关的疾病，以及其他由淋巴细胞减少或S1P受体调节的疾病。
• EP1981837A2
  申请人：——

  公开号：EP1981837A2

  公开（公告）日：2008-10-22