4-methyl-2-(6-(4-methyl-1-(4-(trifluoromethyl)piperidin-1-yl)pentyl)-4'-(trifluoromethyl)biphenyl-3-yl)pentanoic acid | 1257396-03-4

• 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: 4-methyl-2-(6-(4-methyl-1-(4-(trifluoromethyl)piperidin-1-yl)pentyl)-4'-(trifluoromethyl)biphenyl-3-yl)pentanoic acid
• 英文别名: 4-Methyl-2-[4-[4-methyl-1-[4-(trifluoromethyl)piperidin-1-yl]pentyl]-3-[4-(trifluoromethyl)phenyl]phenyl]pentanoic acid
• CAS: 1257396-03-4
• 化学式: C₃₁H₃₉F₆NO₂
• 分子量: 571.647
• InChiKey: WKMYZLUKGGFMOA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  40
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  40.5
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  2-(3-羟基苯基)-4-甲基戊酸甲酯 在 吡啶 、 甲醇 、 sodium tetrahydroborate 、 四(三苯基膦)钯 、 三氟化硼乙醚 、 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 3.84h， 生成 4-methyl-2-(6-(4-methyl-1-(4-(trifluoromethyl)piperidin-1-yl)pentyl)-4'-(trifluoromethyl)biphenyl-3-yl)pentanoic 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

文献信息

• 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.