1-[(1S)-1-(4-fluorophenyl)ethyl]-3-[hydroxy-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methyl]-5-[(4-methoxyphenyl)methoxymethyl]pyridin-2-one | 1128103-55-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-[(1S)-1-(4-fluorophenyl)ethyl]-3-[hydroxy-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methyl]-5-[(4-methoxyphenyl)methoxymethyl]pyridin-2-one
• CAS: 1128103-55-8
• 化学式: C₃₄H₃₄FN₃O₅
• 分子量: 583.659
• InChiKey: NSVNZMWYCPDJRM-SBYCOZGSSA-N

物化性质

• 沸点：
  793.4±60.0 °C(predicted)
• 密度：
  1.22±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  43
• 可旋转键数：
  11
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  86
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-[(1S)-1-(4-fluorophenyl)ethyl]-3-[hydroxy-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methyl]-5-[(4-methoxyphenyl)methoxymethyl]pyridin-2-one 在 吡啶 、 ammonium cerium (IV) nitrate 、 二乙胺基三氟化硫 、 水 、 戴斯-马丁氧化剂 、 一水合肼 、 三氯氧磷 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 为溶剂， 反应 24.0h， 生成 (S)-5-(fluoromethyl)-7-(1-(4-fluorophenyl)ethyl)-3-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)-7H-pyrazolo[3,4-b]pyridine
  参考文献：
  名称：

  Discovery of a Potent Pyrazolopyridine Series of γ-Secretase Modulators

  摘要：

  The synthesis and structure activity relationship of a novel series of pyrazolopyridines are reported. These compounds represent a new class of gamma-secretase modulators that demonstrate good in vitro potency in inhibiting A beta(42) production. Examples with statistically significant in vivo efficacy in reducing the production of rat cerebrospinal fluid A beta(42) were also identified.

  DOI：

  10.1021/ml2000438
• 作为产物：
  描述：

  2-羟基-3-溴-5-乙酸酯吡啶 在 吡啶 、 sodium tetrahydroborate 、 lithium chloro-isopropyl-magnesium chloride 、 三聚氟氰 、 三丁基膦 、 水 、 sodium hydride 、 sodium hydroxide 、 1,1'-azodicarbonyl-dipiperidine 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 87.3h， 生成 1-[(1S)-1-(4-fluorophenyl)ethyl]-3-[hydroxy-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]methyl]-5-[(4-methoxyphenyl)methoxymethyl]pyridin-2-one
  参考文献：
  名称：

  Discovery of a Potent Pyrazolopyridine Series of γ-Secretase Modulators

  摘要：

  The synthesis and structure activity relationship of a novel series of pyrazolopyridines are reported. These compounds represent a new class of gamma-secretase modulators that demonstrate good in vitro potency in inhibiting A beta(42) production. Examples with statistically significant in vivo efficacy in reducing the production of rat cerebrospinal fluid A beta(42) were also identified.

  DOI：

  10.1021/ml2000438

文献信息

• [EN] GAMMA SECRETASE MODULATORS<br/>[FR] MODULATEURS DE LA GAMMA SÉCRÉTASE
  申请人：SCHERING CORP

  公开号：WO2009032277A1

  公开（公告）日：2009-03-12

  This invention provides novel compounds that are modulators of gamma secretase. The compounds have the formula (I). Also disclosed are methods of modulating gamma secretase activity and methods of treating Alzheimer's Disease using the compounds of formula (I).

  这项发明提供了一种调节γ-分泌酶的新化合物。这些化合物的化学式为（I）。还公开了调节γ-分泌酶活性的方法以及使用化合物（I）治疗阿尔茨海默病的方法。
• GAMMA SECRETASE MODULATORS
  申请人：Huang Xianhai

  公开号：US20110015190A1

  公开（公告）日：2011-01-20

  This invention provides novel compounds that are modulators of gamma secretase. The compounds have the formula (I) wherein R 2 is a fused bicyclic ring of the formula (II). Also disclosed are methods of modulating gamma secretase activity and methods of treating Alzheimer's disease using the compounds of formula (I).

  本发明提供了一种新型化合物，其为γ-分泌酶的调节剂。该化合物的化学式为(I)，其中R2是化学式(II)的融合双环。此外，还揭示了利用化合物(I)调节γ-分泌酶活性和治疗阿尔茨海默病的方法。
• US8450343B2
  申请人：——

  公开号：US8450343B2

  公开（公告）日：2013-05-28
• US8518975B2
  申请人：——

  公开号：US8518975B2

  公开（公告）日：2013-08-27
• Discovery of a Potent Pyrazolopyridine Series of γ-Secretase Modulators
  作者：Jun Qin、Wei Zhou、Xianhai Huang、Pawan Dhondi、Anandan Palani、Robert Aslanian、Zhaoning Zhu、William Greenlee、Mary Cohen-Williams、Nicholas Jones、Lynn Hyde、Lili Zhang

  DOI：10.1021/ml2000438

  日期：2011.6.9

  The synthesis and structure activity relationship of a novel series of pyrazolopyridines are reported. These compounds represent a new class of gamma-secretase modulators that demonstrate good in vitro potency in inhibiting A beta(42) production. Examples with statistically significant in vivo efficacy in reducing the production of rat cerebrospinal fluid A beta(42) were also identified.