1-(4-(octyloxy)-3-(trifluoromethyl)phenyl)ethanone | 1005407-56-6

• 英文名称: 1-(4-(octyloxy)-3-(trifluoromethyl)phenyl)ethanone
• CAS: 1005407-56-6
• 化学式: C₁₇H₂₂BrF₃O₂
• 分子量: 395.26
• InChiKey: PBDLPTDDAZYYOX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.02
• 重原子数：
  23.0
• 可旋转键数：
  10.0
• 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：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  1-(4-(octyloxy)-3-(trifluoromethyl)phenyl)ethanone 在 二甲酰氨基钠 、 盐酸 、 水 作用下， 以 乙腈 为溶剂， 反应 15.0h， 生成 2-amino-1-(4-(octyloxy)-3-(trifluoromethyl)phenyl)ethanone hydrochloride
  参考文献：
  名称：

  WO2008/16692

  摘要：

  公开号：
• 作为产物：
  描述：

  辛醇 在 potassium tert-butylate 、 copper(ll) bromide 作用下， 以 四氢呋喃 、 氯仿 、 乙酸乙酯 为溶剂， 反应 3.75h， 生成 1-(4-(octyloxy)-3-(trifluoromethyl)phenyl)ethanone
  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