triethyl{[(1Z)-1-(2-methylbenzylidene)prop-2-en-1-yl]oxy}silane

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: triethyl{[(1Z)-1-(2-methylbenzylidene)prop-2-en-1-yl]oxy}silane
• 英文别名: triethyl-[(1Z)-1-(2-methylphenyl)buta-1,3-dien-2-yl]oxysilane
• 化学式: C₁₇H₂₆OSi
• 分子量: 274.478
• InChiKey: SUANTFYGBDVGPJ-VKAVYKQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.54
• 重原子数：
  19
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  9.2
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  邻甲基苯乙酸 在 4-二甲氨基吡啶 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 甲苯 、 乙腈 为溶剂， 反应 2.5h， 生成 triethyl{[(1Z)-1-(2-methylbenzylidene)prop-2-en-1-yl]oxy}silane 、 triethyl{[(1E)-1-(2-methylbenzylidene)prop-2-en-1-yl]oxy}silane
  参考文献：
  名称：

  WO2008/124143

  摘要：

  公开号：

文献信息

• 2-[(3a<i>R</i>,4<i>R</i>,5<i>S</i>,7a<i>S</i>)-5-{(1<i>S</i>)-1-[3,5-Bis(trifluoromethyl)phenyl]-2-hydroxyethoxy}-4-(2-methylphenyl)octahydro-2<i>H</i>-isoindol-2-yl]-1,3-oxazol-4(5<i>H</i>)-one: A Potent Human NK₁ Receptor Antagonist with Multiple Clearance Pathways
  作者：Andrew J. Kassick、Jinlong Jiang、Jaime Bunda、David Wilson、Jianming Bao、Huagang Lu、Peter Lin、Richard G. Ball、George A. Doss、Xinchun Tong、Kwei-Lan C. Tsao、Hong Wang、Gary Chicchi、Bindhu Karanam、Richard Tschirret-Guth、Koppara Samuel、Donald F. Hora、Sanjeev Kumar、Maria Madeira、Waisi Eng、Richard Hargreaves、Mona Purcell、Liza Gantert、Jacquelyn Cook、Robert J. DeVita、Sander G. Mills

  DOI：10.1021/jm400751p

  日期：2013.7.25

  Hydroisoindoline 2 has been previously identified as a potent, brain-penetrant NK1 receptor antagonist with a long duration of action and improved profile of CYP3A4 inhibition and induction compared to aprepitant. However, compound 2 is predicted, based on data in preclinical species, to have a human half-life longer than 40 h and likely to have drug-drug-interactions (DDI), as 2 is a victim of CYP3A4 inhibition caused by its exclusive clearance pathway via CYP3A4 oxidation in humans. We now report 2-[(3aR4R,5S,7aS)-5-(1S)-1-[3,5-bis(trifluoromethyl)phenyl]-2-hydroxyethoxy}-4-(2-methylphenypoctahydro-2H-isoindol-2-yl]-1,3-oxazol-4(5H)-one (3) as a next generation NK1 antagonist that possesses an additional clearance pathway through glucuronidation in addition to that via CYP3A4 oxidation. Compound 3 has a much lower propensity for drug drug interactions and a reduced estimated human half-life consistent with once daily dosing. In preclinical species, compound 3 has demonstrated potency, brain penetration, and a safety profile similar to 2, as well as excellent pharmacokinetics.