N-[(4-fluorophenyl)methyl]-3-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-4,5,6,7-tetrahydro-1,2-benzoxazol-7-amine | 1433662-67-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: N-[(4-fluorophenyl)methyl]-3-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-4,5,6,7-tetrahydro-1,2-benzoxazol-7-amine
• CAS: 1433662-67-9
• 化学式: C₂₅H₂₅FN₄O₂
• 分子量: 432.498
• InChiKey: VNHURZWDNQYTCL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  32
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  65.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  3-(4-amino-3-methoxyphenyl)-5,6-dihydrobenzo[d]isoxazol-7(4H)-one 在 titanium(IV) isopropylate 、 ammonium acetate 、 乙酸酐 、 caesium carbonate 、 溶剂黄146 、 potassium iodide 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 生成 N-[(4-fluorophenyl)methyl]-3-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-4,5,6,7-tetrahydro-1,2-benzoxazol-7-amine
  参考文献：
  名称：

  Discovery of a Tetrahydrobenzisoxazole Series of γ-Secretase Modulators

  摘要：

  The design and synthesis of a new series of tetrahydrobenzisoxazoles as modulators of gamma-secretase activity and their structure-activity relationship (SAR) will be detailed. Several compounds are active y-secretase modulators (GSMs) with good to excellent selectivity for the reduction of A beta(42) in the cellular assay. Compound 14a was tested in vivo in a nontransgenic rat model and was found to significantly reduce A beta(42), in the CNS compartment compared to vehicle-treated animals (up to 58% reduction of cerebrospinal fluid A beta(42) as measured 3 h after an acute oral dosing at 30 mg/kg).

  DOI：

  10.1021/acsmedchemlett.7b00178

文献信息

• [EN] GAMMA SECRETASE MODULATORS<br/>[FR] MODULATEURS DE LA GAMMA-SÉCRÉTASE
  申请人：MERCK SHARP & DOHME

  公开号：WO2013066740A1

  公开（公告）日：2013-05-10

  Disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein each of the substituents is given the definition as set forth in the specification and claims. Also disclosed are pharmaceutical compositions containing compounds of Formula (I) and use of the compounds in the treatment of neurodegenerative diseases or conditions such as Alzheimer's disease.

  本文披露了式（I）的化合物及其药用盐，其中每个取代基的定义如规范和索赔中所述。还披露了含有式（I）化合物的药物组合物，以及利用这些化合物治疗神经退行性疾病或病症，如阿尔茨海默病。
• GAMMA SECRETASE MODULATORS
  申请人：MERCK SHARP & DOHME CORP.

  公开号：US20140296311A1

  公开（公告）日：2014-10-02

  Disclosed herein are compounds of Formula (I) and pharmaceutically acceptable salts thereof, wherein each of the substituents is given the definition as set forth in the specification and claims. Also disclosed are pharmaceutical compositions containing compounds of Formula (I) and use of the compounds in the treatment of neurodegenerative diseases or conditions such as Alzheimer's disease.

  本文披露了公式（I）的化合物及其药物可接受的盐，其中每个取代基的定义如规范和权利要求所述。还披露了包含公式（I）化合物的药物组合物以及使用这些化合物治疗神经退行性疾病或状况，例如阿尔茨海默病。
• US9096582B2
  申请人：——

  公开号：US9096582B2

  公开（公告）日：2015-08-04
• Discovery of a Tetrahydrobenzisoxazole Series of γ-Secretase Modulators
  作者：Zhiqiang Zhao、Dmitri A. Pissarnitski、Xianhai Huang、Anandan Palani、Zhaoning Zhu、William J. Greenlee、Lynn A. Hyde、Lixin Song、Giuseppe Terracina、Lili Zhang、Eric M. Parker

  DOI：10.1021/acsmedchemlett.7b00178

  日期：2017.10.12

  The design and synthesis of a new series of tetrahydrobenzisoxazoles as modulators of gamma-secretase activity and their structure-activity relationship (SAR) will be detailed. Several compounds are active y-secretase modulators (GSMs) with good to excellent selectivity for the reduction of A beta(42) in the cellular assay. Compound 14a was tested in vivo in a nontransgenic rat model and was found to significantly reduce A beta(42), in the CNS compartment compared to vehicle-treated animals (up to 58% reduction of cerebrospinal fluid A beta(42) as measured 3 h after an acute oral dosing at 30 mg/kg).