2-(3-bromo-5-methylphenyl)propanenitrile | 1161361-97-2

• 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: 2-(3-bromo-5-methylphenyl)propanenitrile
• CAS: 1161361-97-2
• 化学式: C₁₀H₁₀BrN
• 分子量: 224.1
• InChiKey: RSMKTYXYIZKHNZ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  12
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  23.8
• 氢给体数：
  0
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  2-(3-bromo-5-methylphenyl)propanenitrile 在 三乙基硅烷 、 二(三叔丁基膦)钯 、 sodium hydride 、 sodium carbonate 、 三氟乙酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 二氯甲烷 、 mineral oil 为溶剂， 反应 6.83h， 生成 2-methyl-2-[3-methyl-5-(1H-pyrazolo[3,4-b]pyridin-4-yl)phenyl]butanenitrile
  参考文献：
  名称：

  Discovery of Selective, Orally Bioavailable Pyrazolopyridine Inhibitors of Protein Kinase Cθ (PKCθ) That Ameliorate Symptoms of Experimental Autoimmune Encephalomyelitis

  摘要：

  PKC theta plays an important role in T cell biology and is a validated target for a number of disease states. A series of potent and selective PKC theta inhibitors were designed and synthesized starting from a HTS hit compound. Cell activity, while initially a challenge to achieve, was built into the series by transforming the nitrile unit of the scaffold into a primary amine, the latter predicted to form a new hydrogen bond to Asp508 near the entrance of the ATP binding site of PKC theta. Significant improvements in physiochemical parameters were observed on introduction of an oxetane group proximal to a primary amine leading to compound 22, which demonstrated a reduction of symptoms in a mouse model of multiple sclerosis.

  DOI：

  10.1021/acsmedchemlett.9b00134
• 作为产物：
  描述：

  1-溴-3-(溴甲基)-5-甲基苯 在 sodium hydride 作用下， 以 四氢呋喃 、 水 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 5.83h， 生成 2-(3-bromo-5-methylphenyl)propanenitrile
  参考文献：
  名称：

  Discovery of Selective, Orally Bioavailable Pyrazolopyridine Inhibitors of Protein Kinase Cθ (PKCθ) That Ameliorate Symptoms of Experimental Autoimmune Encephalomyelitis

  摘要：

  PKC theta plays an important role in T cell biology and is a validated target for a number of disease states. A series of potent and selective PKC theta inhibitors were designed and synthesized starting from a HTS hit compound. Cell activity, while initially a challenge to achieve, was built into the series by transforming the nitrile unit of the scaffold into a primary amine, the latter predicted to form a new hydrogen bond to Asp508 near the entrance of the ATP binding site of PKC theta. Significant improvements in physiochemical parameters were observed on introduction of an oxetane group proximal to a primary amine leading to compound 22, which demonstrated a reduction of symptoms in a mouse model of multiple sclerosis.

  DOI：

  10.1021/acsmedchemlett.9b00134

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 Selective, Orally Bioavailable Pyrazolopyridine Inhibitors of Protein Kinase Cθ (PKCθ) That Ameliorate Symptoms of Experimental Autoimmune Encephalomyelitis
  作者：Philip N. Collier、Heather C. Twin、Ronald M. A. Knegtel、Dean Boyall、Guy Brenchley、Christopher J. Davis、Shazia Keily、Chau Mak、Andrew Miller、Françoise Pierard、Luca Settimo、Clare M. Bolton、Peter Chiu、Adam Curnock、Elisabeth Doyle、Adam J. Tanner、Juan-Miguel Jimenez

  DOI：10.1021/acsmedchemlett.9b00134

  日期：2019.8.8

  PKC theta plays an important role in T cell biology and is a validated target for a number of disease states. A series of potent and selective PKC theta inhibitors were designed and synthesized starting from a HTS hit compound. Cell activity, while initially a challenge to achieve, was built into the series by transforming the nitrile unit of the scaffold into a primary amine, the latter predicted to form a new hydrogen bond to Asp508 near the entrance of the ATP binding site of PKC theta. Significant improvements in physiochemical parameters were observed on introduction of an oxetane group proximal to a primary amine leading to compound 22, which demonstrated a reduction of symptoms in a mouse model of multiple sclerosis.