methyl 2-(3-(benzyloxy)phenyl)propanoate | 141258-14-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: methyl 2-(3-(benzyloxy)phenyl)propanoate
• 英文别名: methyl 2-(3-benzyloxyphenyl)propanoate；methyl 2-(3-phenylmethoxyphenyl)propanoate
• CAS: 141258-14-2
• 化学式: C₁₇H₁₈O₃
• 分子量: 270.328
• InChiKey: NRUBTVWZKFJHCQ-UHFFFAOYSA-N

物化性质

• 沸点：
  377.8±30.0 °C(Predicted)
• 密度：
  1.106±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  20
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  35.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl 2-(3-(benzyloxy)phenyl)propanoate 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 、 magnesium chloride 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 3.0h， 生成 2-(4-甲酰基-3-羟基苯)丙酸甲酯
  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：

  3-羟基苯乙酸甲酯 在 potassium carbonate 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 24.0h， 生成 methyl 2-(3-(benzyloxy)phenyl)propanoate
  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 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.
• WO2007/58504
  申请人：——

  公开号：——

  公开（公告）日：——
• Synthesis of (±)-aphanorphine via an aminylium ion intermediate
  作者：Toshio Honda、Atsunori Yamamoto、Yingshe Cui、Masayoshi Tsubuki

  DOI：10.1039/p19920000531

  日期：——

  A facile synthesis of (+/-)-aphanorphine 1 was achieved via the aminylium ion intermediate as a reactive species.
• [EN] NOVEL COMPOUNDS AS AGONIST FOR PPAR GAMMA AND PPAR ALPHA, METHOD FOR PREPARATION OF THE SAME, AND PHARMACEUTICAL COMPOSITION CONTAINING THE SAME<br/>[FR] NOUVEAUX COMPOSES UTILISES COMME AGONISTES DES PPAR GAMMA ET DES PPAR ALPHA, PROCEDE DE PREPARATION AFFERENT ET COMPOSITION PHARMACEUTIQUE LES RENFERMANT
  申请人：LG LIFE SCIENCES LTD

  公开号：WO2007058504A1

  公开（公告）日：2007-05-24

  [EN] The present invention relates to novel compounds accelerating the activity of Peroxisome proliferator-activated receptor gamma (PPAR?) and alpha (PPARa), processes of preparing the same, and pharmaceutical compositions containing the same as an active agent.
  [FR] L'invention porte sur de nouveaux composés accélérant l'activité des récepteurs gamma (PPAR?) et alpha (PPARa) activés par les proliférateurs des péroxysomes, sur des procédés de préparation afférents et sur des compositions pharmaceutiques les renfermant en tant qu'agent actif.