2-(3,5-bis(trifluoromethyl)phenyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)acetamide | 1161361-85-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 2-(3,5-bis(trifluoromethyl)phenyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)acetamide
• 英文别名: 2-[3,5-bis(trifluoromethyl)phenyl]-N-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]acetamide
• CAS: 1161361-85-8
• 化学式: C₂₁H₁₇F₆N₃O₂
• 分子量: 457.375
• InChiKey: YRTAZAMKCJZAPT-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  32
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  56.2
• 氢给体数：
  1
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  3-甲氧基-4-(4-甲基-1H-咪唑-1-基)苯胺 、 3,5-双(三氟甲基)苯乙酸 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 20.0h， 生成 2-(3,5-bis(trifluoromethyl)phenyl)-N-(3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl)acetamide
  参考文献：
  名称：

  [EN] GAMMA SECRETASE MODULATORS
  [FR] MODULATEURS DE LA GAMMA-SÉCRÉTASE

  摘要：

  本发明提供了作为γ-分泌酶调节剂的化合物，因此可用于治疗可通过调节γ-分泌酶治疗的疾病，如阿尔茨海默病。还提供了含有此类化合物的药物组合物以及制备此类化合物的过程。

  公开号：

  WO2009075874A1

文献信息

• [EN] GAMMA SECRETASE MODULATORS<br/>[FR] MODULATEURS DE LA GAMMA-SÉCRÉTASE
  申请人：AMGEN INC

  公开号：WO2009075874A1

  公开（公告）日：2009-06-18

  The present invention provides compounds that are gamma secretase modulators and are therefore useful for the treatment of diseases treatable by modulation of gamma secretase such as Alzheimer's disease. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

  本发明提供了作为γ-分泌酶调节剂的化合物，因此可用于治疗可通过调节γ-分泌酶治疗的疾病，如阿尔茨海默病。还提供了含有此类化合物的药物组合物以及制备此类化合物的过程。
• Gamma Secretase Modulators
  申请人：Hitchcock Stephen A.

  公开号：US20110166132A1

  公开（公告）日：2011-07-07

  The present invention provides compounds that are gamma secretase modulators and are therefore useful for the treatment of diseases treatable by modulation of gamma secretase such as Alzheimer's disease. Also provided are pharmaceutical compositions containing such compounds and processes for preparing such compounds.

  本发明提供的化合物是伽马分泌酶调节剂，因此可用于治疗可通过伽马分泌酶调节治疗的疾病，例如阿尔茨海默病。还提供了包含这些化合物的药物组合物以及制备这些化合物的过程。
• GAMMA SECRETASE MODULATORS
  申请人：Amgen, Inc

  公开号：EP2231602A1

  公开（公告）日：2010-09-29
• Discovery of 2-methylpyridine-based biaryl amides as γ-secretase modulators for the treatment of Alzheimer’s disease
  作者：Jian Jeffrey Chen、Wenyuan Qian、Kaustav Biswas、Chester Yuan、Albert Amegadzie、Qingyian Liu、Thomas Nixey、Joe Zhu、Mqhele Ncube、Robert M. Rzasa、Frank Chavez、Ning Chen、Frenel DeMorin、Shannon Rumfelt、Christopher M. Tegley、Jennifer R. Allen、Stephen Hitchcock、Randy Hungate、Michael D. Bartberger、Leeanne Zalameda、Yichin Liu、John D. McCarter、Jianhua Zhang、Li Zhu、Safura Babu-Khan、Yi Luo、Jodi Bradley、Paul H. Wen、Darren L. Reid、Frank Koegler、Charles Dean、Dean Hickman、Tiffany L. Correll、Toni Williamson、Stephen Wood

  DOI：10.1016/j.bmcl.2013.09.041

  日期：2013.12

  gamma-Secretase modulators (GSMs) are potentially disease-modifying treatments for Alzheimer's disease. They selectively lower pathogenic A beta 42 levels by shifting the enzyme cleavage sites without inhibiting gamma-secretase activity, possibly avoiding known adverse effects observed with complete inhibition of the enzyme complex. A cell-based HTS effort identified the sulfonamide 1 as a GSM lead. Lead optimization studies identified compound 25 with improved cell potency, PKDM properties, and it lowered A beta 42 levels in the cerebrospinal fluid ( CSF) of Sprague-Dawley rats following oral administration. Further optimization of 25 to improve cellular potency is described. (C) 2013 Elsevier Ltd. All rights reserved.