methyl 2-(4-(4-methylpentanoyl)-3-(trifluoromethylsulfonyloxy)phenyl)acetate | 1257397-75-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: methyl 2-(4-(4-methylpentanoyl)-3-(trifluoromethylsulfonyloxy)phenyl)acetate
• 英文别名: Methyl 2-(4-(4-methylpentanoyl)-3-(trifluoromethylsulfonyloxy)phenyl)acetate；methyl 2-[4-(4-methylpentanoyl)-3-(trifluoromethylsulfonyloxy)phenyl]acetate
• CAS: 1257397-75-3
• 化学式: C₁₆H₁₉F₃O₆S
• 分子量: 396.384
• InChiKey: ZFFXTZUSFQYPLR-UHFFFAOYSA-N

物化性质

• 沸点：
  454.5±45.0 °C(Predicted)
• 密度：
  1.314±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  95.1
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  methyl 2-(4-(4-methylpentanoyl)-3-(trifluoromethylsulfonyloxy)phenyl)acetate 在 甲醇 、 sodium tetrahydroborate 、 四(三苯基膦)钯 、 三溴化磷 、 碳酸氢钠 、 potassium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙二醇二甲醚 、 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.67h， 生成 2-(6-(1-(4-tert-butylcyclohexylamino)-4-methylpentyl)-4'-(trifluoromethyl)biphenyl-3-yl)acetic acid
  参考文献：
  名称：

  Discovery of 4-aminomethylphenylacetic acids as γ-secretase modulators via a scaffold design approach

  摘要：

  Starting from literature examples of nonsteroidal anti-inflammatory drugs (NSAIDs)-type carboxylic acid gamma-secretase modulators (GSMs) and using a scaffold design approach, we identified 4-aminomethylphenylacetic acid 4 with a desirable gamma-secretase modulation profile. Scaffold optimization led to the discovery of a novel chemical series, represented by 6b, having improved brain penetration. Further SAR studies provided analog 6q that exhibited a good pharmacological profile. Oral administration of 6q significantly reduced brain A beta 42 levels in mice and rats. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.047
• 作为产物：
  描述：

  3-羟基苯乙酸甲酯 在 吡啶 、 三氟化硼乙醚 作用下， 以 二氯甲烷 为溶剂， 反应 1.17h， 生成 methyl 2-(4-(4-methylpentanoyl)-3-(trifluoromethylsulfonyloxy)phenyl)acetate
  参考文献：
  名称：

  Discovery of 4-aminomethylphenylacetic acids as γ-secretase modulators via a scaffold design approach

  摘要：

  Starting from literature examples of nonsteroidal anti-inflammatory drugs (NSAIDs)-type carboxylic acid gamma-secretase modulators (GSMs) and using a scaffold design approach, we identified 4-aminomethylphenylacetic acid 4 with a desirable gamma-secretase modulation profile. Scaffold optimization led to the discovery of a novel chemical series, represented by 6b, having improved brain penetration. Further SAR studies provided analog 6q that exhibited a good pharmacological profile. Oral administration of 6q significantly reduced brain A beta 42 levels in mice and rats. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.10.047

文献信息

• [EN] CARBOXYLIC ACID-CONTAINING COMPOUNDS, DERIVATIVES THEREOF, AND RELATED METHODS OF USE<br/>[FR] COMPOSÉS CONTENANT DE L'ACIDE CARBOXYLIQUE, LEURS DÉRIVÉS ET PROCÉDÉS D'UTILISATION ASSOCIÉS
  申请人：BIOGEN IDEC INC

  公开号：WO2010138901A1

  公开（公告）日：2010-12-02

  Compounds that modulate gamma secretase (e.g., alter the cleavage pattern of gamma secretase) are described herein. Also disclosed are pharmaceutical compositions, methods of modulating the activity of gamma secretase, and methods of treating Alzheimer's Disease using the compounds described herein.

  本文件描述了调节γ-分泌酶（例如，改变γ-分泌酶的切割模式）的化合物。还公开了包含这些化合物的药物组合物、调节γ-分泌酶活性的方法，以及使用本文件描述的化合物治疗阿尔茨海默病的方法。
• Discovery of 4-aminomethylphenylacetic acids as γ-secretase modulators via a scaffold design approach
  作者：Zhili Xin、Hairuo Peng、Andrew Zhang、Tina Talreja、Gnanasambandam Kumaravel、Lin Xu、Ellen Rohde、Mi-yong Jung、Melanie N. Shackett、David Kocisko、Sowmya Chollate、Anthone W. Dunah、Pamela A. Snodgrass-Belt、H. Moore Arnold、Arthur G. Taveras、Kenneth J. Rhodes、Robert H. Scannevin

  DOI：10.1016/j.bmcl.2011.10.047

  日期：2011.12

  Starting from literature examples of nonsteroidal anti-inflammatory drugs (NSAIDs)-type carboxylic acid gamma-secretase modulators (GSMs) and using a scaffold design approach, we identified 4-aminomethylphenylacetic acid 4 with a desirable gamma-secretase modulation profile. Scaffold optimization led to the discovery of a novel chemical series, represented by 6b, having improved brain penetration. Further SAR studies provided analog 6q that exhibited a good pharmacological profile. Oral administration of 6q significantly reduced brain A beta 42 levels in mice and rats. (C) 2011 Elsevier Ltd. All rights reserved.