[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-(2-methyl-2H-indazol-7-yl)amine | 1259032-82-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: [3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-(2-methyl-2H-indazol-7-yl)amine
• 英文别名: N-[3-methoxy-4-(4-methyl-1H-imidazol-1-yl)phenyl]-2-methyl-2H-indazol-7-amine；N-[3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-2-methylindazol-7-amine
• CAS: 1259032-82-0
• 化学式: C₁₉H₁₉N₅O
• 分子量: 333.393
• InChiKey: VFBJOWURJQKUOE-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  56.9
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-溴-6-甲基苯胺 在 盐酸 、 tris-(dibenzylideneacetone)dipalladium(0) 、 potassium tert-butylate 、 caesium carbonate 、 sodium nitrite 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 水 、 二甲基亚砜 、 甲苯 、 叔丁醇 为溶剂， 反应 38.5h， 生成 [3-methoxy-4-(4-methylimidazol-1-yl)phenyl]-(2-methyl-2H-indazol-7-yl)amine
  参考文献：
  名称：

  Design and Synthesis of a Novel Series of Bicyclic Heterocycles As Potent γ-Secretase Modulators

  摘要：

  The design and the synthesis of several chemical subclasses of imidazole containing gamma-secretase modulators (GSMs) is described. Conformational restriction of pyridone 4 into bicyclic pyridone isosteres has led to compounds with high in vitro and in vivo potency. This has resulted, in the identification of benzimidazole 44a as a GSM with low nanomolar potency in vitro. In mouse, rat, and dog, this compound displayed the typical gamma-secretase modulatory profile by lowering A beta 42 and A beta 40 levels combined with an especially pronounced increase in A beta 38 and A beta 37 levels while leaving the total levels of amyloid peptides unchanged.

  DOI：

  10.1021/jm201710f

文献信息

• SUBSTITUTED INDAZOLE AND AZA-INDAZOLE DERIVATIVES AS GAMMA SECRETASE MODULATORS
  申请人：Janssen Pharmaceuticals, Inc.

  公开号：EP2427453B1

  公开（公告）日：2013-07-17
• NOVEL SUBSTITUTED INDAZOLE AND AZA-INDAZOLE DERIVATIVES AS GAMMA SECRETASE MODULATORS
  申请人：Bischoff François Paul

  公开号：US20120095036A1

  公开（公告）日：2012-04-19

  The present invention is concerned with novel substituted indazole and aza-indazole derivatives of Formula (I) wherein R 1 , R 2 , R 3 , R 4 , Y, A 1 , A 2 , A 3 , A 4 , X 1 , X 2 , X 3 and Het 1 have the meaning defined in the claims. The compounds according to the present invention are useful as gamma secretase modulators. The invention further relates to processes for preparing such novel compounds, pharmaceutical compositions comprising said compounds as an active ingredient as well as the use of said compounds as a medicament.
• US8835482B2
  申请人：——

  公开号：US8835482B2

  公开（公告）日：2014-09-16
• Design and Synthesis of a Novel Series of Bicyclic Heterocycles As Potent γ-Secretase Modulators
  作者：Francois Bischoff、Didier Berthelot、Michel De Cleyn、Gregor Macdonald、Garrett Minne、Daniel Oehlrich、Serge Pieters、Michel Surkyn、Andrés A. Trabanco、Gary Tresadern、Sven Van Brandt、Ingrid Velter、Mirko Zaja、Herman Borghys、Chantal Masungi、Marc Mercken、Harrie J. M. Gijsen

  DOI：10.1021/jm201710f

  日期：2012.11.8

  The design and the synthesis of several chemical subclasses of imidazole containing gamma-secretase modulators (GSMs) is described. Conformational restriction of pyridone 4 into bicyclic pyridone isosteres has led to compounds with high in vitro and in vivo potency. This has resulted, in the identification of benzimidazole 44a as a GSM with low nanomolar potency in vitro. In mouse, rat, and dog, this compound displayed the typical gamma-secretase modulatory profile by lowering A beta 42 and A beta 40 levels combined with an especially pronounced increase in A beta 38 and A beta 37 levels while leaving the total levels of amyloid peptides unchanged.