N1-benzyl-3-bromo-benzene-1,2-diamine | 920285-22-9

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N1-benzyl-3-bromo-benzene-1,2-diamine
• 英文别名: 1-N-benzyl-3-bromobenzene-1,2-diamine
• CAS: 920285-22-9
• 化学式: C₁₃H₁₃BrN₂
• 分子量: 277.164
• InChiKey: KVQABCCPHXLDFI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  38
• 氢给体数：
  2
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  N1-benzyl-3-bromo-benzene-1,2-diamine 在 溶剂黄146 、 sodium nitrite 作用下， 反应 3.0h， 生成 1-benzyl-4-bromo-1H-benzotriazole
  参考文献：
  名称：

  Fragment Based Optimization of Metabotropic Glutamate Receptor 2 (mGluR2) Positive Allosteric Modulators in the Absence of Structural Information

  摘要：

  Metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulators (PAMs) have been implicated as potential pharmacotherapy for psychiatric conditions. Screening our corporate compound deck, we identified a benzotriazole fragment (4) that was rapidly optimized to a potent and metabolically stable early lead (16). The highly lipophilic character of 16, together with its limited solubility, permeability, and high protein binding, however, did not allow reaching of the proof of concept in vivo. Since further attempts on the optimization of druglike properties were unsuccessful, the original hit 4 has been revisited and was optimized following the principles of fragment based drug discovery (FBDD). Lacking structural information on the receptor ligand complex, we implemented a group efficiency (GE) based strategy and identified a new fragment like lead (60) with more balanced profile. Significant improvement achieved on the druglike properties nominated the compound for in vivo proof of concept studies that revealed the chemotype being a promising PAM lead targeting mGluR2 receptors.

  DOI：

  10.1021/acs.jmedchem.8b00161
• 作为产物：
  描述：

  2-溴-6-氟硝基苯 在 盐酸 、 potassium carbonate 、 tin(ll) chloride 作用下， 以 甲醇 、 乙腈 为溶剂， 反应 30.0h， 生成 N1-benzyl-3-bromo-benzene-1,2-diamine
  参考文献：
  名称：

  Fragment Based Optimization of Metabotropic Glutamate Receptor 2 (mGluR2) Positive Allosteric Modulators in the Absence of Structural Information

  摘要：

  Metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulators (PAMs) have been implicated as potential pharmacotherapy for psychiatric conditions. Screening our corporate compound deck, we identified a benzotriazole fragment (4) that was rapidly optimized to a potent and metabolically stable early lead (16). The highly lipophilic character of 16, together with its limited solubility, permeability, and high protein binding, however, did not allow reaching of the proof of concept in vivo. Since further attempts on the optimization of druglike properties were unsuccessful, the original hit 4 has been revisited and was optimized following the principles of fragment based drug discovery (FBDD). Lacking structural information on the receptor ligand complex, we implemented a group efficiency (GE) based strategy and identified a new fragment like lead (60) with more balanced profile. Significant improvement achieved on the druglike properties nominated the compound for in vivo proof of concept studies that revealed the chemotype being a promising PAM lead targeting mGluR2 receptors.

  DOI：

  10.1021/acs.jmedchem.8b00161

文献信息

• Benzimidazolone and dihydroindolone derivatives and uses thereof
  申请人：Owens Timothy

  公开号：US20070015744A1

  公开（公告）日：2007-01-18

  Compounds of the formula I: or pharmaceutically acceptable salts thereof wherein m, n, X, Ar, R 1 , R 2 , R 3 , R 4 and R 5 are as defined herein. Also provided are methods for preparing, compositions comprising, and methods for using compounds of formula I.

  式I的化合物： 或其药学上可接受的盐，其中m、n、X、Ar、R1、R2、R3、R4和R5如本文所定义。还提供了制备方法、包含化合物I的组合物以及使用式I化合物的方法。
• US7582760B2
  申请人：——

  公开号：US7582760B2

  公开（公告）日：2009-09-01
• [EN] BENZIMIDAZOLE DERIVATIVES AS 5-HT6,5-HT24<br/>[FR] DERIVES DE BENZIMIDAZOLE TELS QUE 5-HT6, 5-HT24
  申请人：HOFFMANN LA ROCHE

  公开号：WO2007006677A1

  公开（公告）日：2007-01-18

  [EN] Compounds of the formula I: or pharmaceutically acceptable salts thereof wherein m, n, X, Ar, R¹, R², R³, R⁴ and R⁵ are as defined herein. Also provided are methods for preparing, compositions comprising, and methods for using compounds of formula I.
  [FR] L'invention concerne des composés représentés par la formule I, ou des sels pharmaceutiquement acceptables de ces derniers. Dans ladite formule, m, n, X, Ar, R¹, R², R³, R⁴et R⁵ sont tels que définis dans la description. L'invention concerne également des procédés de préparation, des compositions comprenant et des méthodes d'utilisation des composés représentés par la formule I.
• Fragment Based Optimization of Metabotropic Glutamate Receptor 2 (mGluR2) Positive Allosteric Modulators in the Absence of Structural Information
  作者：György Szabó、György I. Túrós、Sándor Kolok、Mónika Vastag、Zsuzsanna Sánta、Miklós Dékány、György I. Lévay、István Greiner、Minami Natsumi、Watanabe Tatsuya、György M. Keserű

  DOI：10.1021/acs.jmedchem.8b00161

  日期：2019.1.10

  Metabotropic glutamate receptor 2 (mGluR2) positive allosteric modulators (PAMs) have been implicated as potential pharmacotherapy for psychiatric conditions. Screening our corporate compound deck, we identified a benzotriazole fragment (4) that was rapidly optimized to a potent and metabolically stable early lead (16). The highly lipophilic character of 16, together with its limited solubility, permeability, and high protein binding, however, did not allow reaching of the proof of concept in vivo. Since further attempts on the optimization of druglike properties were unsuccessful, the original hit 4 has been revisited and was optimized following the principles of fragment based drug discovery (FBDD). Lacking structural information on the receptor ligand complex, we implemented a group efficiency (GE) based strategy and identified a new fragment like lead (60) with more balanced profile. Significant improvement achieved on the druglike properties nominated the compound for in vivo proof of concept studies that revealed the chemotype being a promising PAM lead targeting mGluR2 receptors.