Methyl 2-(3-hydroxyphenyl)pentanoate | 1257397-48-0

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: Methyl 2-(3-hydroxyphenyl)pentanoate
• CAS: 1257397-48-0
• 化学式: C₁₂H₁₆O₃
• 分子量: 208.257
• InChiKey: HGGWDQNGCXCIER-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  46.5
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  Methyl 2-(3-hydroxyphenyl)pentanoate 在 吡啶 、 四(三苯基膦)钯 、 水 、 sodium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 、 甲苯 、 2,3,4-三氟甲苯 为溶剂， 生成 2-{6-[(4-fluorophenyl)(piperidin-1-yl)methyl]-4'-(trifluoromethyl)biphenyl-3-yl}pentanoic acid
  参考文献：
  名称：

  Discovery of BIIB042, a Potent, Selective, and Orally Bioavailable γ-Secretase Modulator

  摘要：

  We have investigated a novel series of acid-derived gamma-secretase modulators as a potential treatment of Alzheimer's disease. Optimization based on cellular potency and brain pharmacodynamics after oral dosing led to the discovery of 10a (BIIB042). Compound 10a is a potent gamma-secretase modulator, which lowered A beta 42, increased A beta 38, but had little to no effect on A beta 40 levels both in vitro and in vivo. In addition, compound 10a did not affect Notch signaling in our in vitro assessment. Compound 10a demonstrated excellent pharmacokinetic parameters in multiple species. Oral administration of 10a significantly reduced brain A beta 42 levels in CF-1 mice and Fischer rats, as well as plasma A beta 42 levels in cynomolgus monkeys. Compound 10a was selected as a candidate for preclinical safety evaluation.

  DOI：

  10.1021/ml200175q
• 作为产物：
  描述：

  2-(3-(苄氧基)苯基)乙酸甲酯 在 palladium 10% on activated carbon 、 氢气 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 生成 Methyl 2-(3-hydroxyphenyl)pentanoate
  参考文献：
  名称：

  Discovery of BIIB042, a Potent, Selective, and Orally Bioavailable γ-Secretase Modulator

  摘要：

  We have investigated a novel series of acid-derived gamma-secretase modulators as a potential treatment of Alzheimer's disease. Optimization based on cellular potency and brain pharmacodynamics after oral dosing led to the discovery of 10a (BIIB042). Compound 10a is a potent gamma-secretase modulator, which lowered A beta 42, increased A beta 38, but had little to no effect on A beta 40 levels both in vitro and in vivo. In addition, compound 10a did not affect Notch signaling in our in vitro assessment. Compound 10a demonstrated excellent pharmacokinetic parameters in multiple species. Oral administration of 10a significantly reduced brain A beta 42 levels in CF-1 mice and Fischer rats, as well as plasma A beta 42 levels in cynomolgus monkeys. Compound 10a was selected as a candidate for preclinical safety evaluation.

  DOI：

  10.1021/ml200175q

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 BIIB042, a Potent, Selective, and Orally Bioavailable γ-Secretase Modulator
  作者：Hairuo Peng、Tina Talreja、Zhili Xin、J. Hernan Cuervo、Gnanasambandam Kumaravel、Michael J. Humora、Lin Xu、Ellen Rohde、Lawrence Gan、Mi-young Jung、Melanie N. Shackett、Sowmya Chollate、Anthone W. Dunah、Pamela A. Snodgrass-belt、H. Moore Arnold、Arthur G. Taveras、Kenneth J. Rhodes、Robert H. Scannevin

  DOI：10.1021/ml200175q

  日期：2011.10.13

  We have investigated a novel series of acid-derived gamma-secretase modulators as a potential treatment of Alzheimer's disease. Optimization based on cellular potency and brain pharmacodynamics after oral dosing led to the discovery of 10a (BIIB042). Compound 10a is a potent gamma-secretase modulator, which lowered A beta 42, increased A beta 38, but had little to no effect on A beta 40 levels both in vitro and in vivo. In addition, compound 10a did not affect Notch signaling in our in vitro assessment. Compound 10a demonstrated excellent pharmacokinetic parameters in multiple species. Oral administration of 10a significantly reduced brain A beta 42 levels in CF-1 mice and Fischer rats, as well as plasma A beta 42 levels in cynomolgus monkeys. Compound 10a was selected as a candidate for preclinical safety evaluation.