2-(3,5-Dimethylphenoxy)-4-chlor-pyridin | 28373-77-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-(3,5-Dimethylphenoxy)-4-chlor-pyridin
• 英文别名: 4-Chloro-2-(3,5-dimethylphenoxy)pyridine
• CAS: 28373-77-5
• 化学式: C₁₃H₁₂ClNO
• 分子量: 233.697
• InChiKey: QLDVDBDPCYMRRB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  22.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-(3,5-Dimethylphenoxy)-4-chlor-pyridin 在 正丁基锂 、 三氟乙酸 作用下， 以 乙二醇二甲醚 、 正己烷 、 二氯甲烷 为溶剂， 反应 8.34h， 生成 2-(3,5-Dimethylphenoxy)-4-(5-methyl-3-piperidin-4-yltriazol-4-yl)pyridine
  参考文献：
  名称：

  Systematically Mitigating the p38α Activity of Triazole-based BET Inhibitors

  摘要：

  The Bromodomain and Extra Terminal (BET) family of proteins recognize post-translational N-ε-acetylated lysine modifications, regulating transcription as "reader" proteins. Bromodomain inhibitors are interesting targets for the development of potential cancer, inflammation, and heart disease treatments. Several dual kinase-bromodomain inhibitors have been identified by screening kinase inhibitor libraries against BET proteins. Although potentially useful from a polypharmacology standpoint, multitarget binding complicates deciphering molecular mechanisms. This report describes a systematic approach to mitigating kinase activity in a dual kinase-bromodomain inhibitor based on a 1,2,3-triazole-pyrimidine core. By modifying the triazole substituent and altering the pyrimidine core, this structure-activity relationship study enhanced BET activity while reducing the p38α kinase activity >90,000-fold. A BRD4-D1 cocrystal structure indicates that the 1,2,3-triazole is acting as a N-ε-acetylated lysine mimic. A BRD4 sensitive cell line, MM.1S, was used to demonstrate activity in cells, which is further supported by reduced c-Myc expression.

  DOI：

  10.1021/acsmedchemlett.9b00227
• 作为产物：
  描述：

  2,4-二氯吡啶 、 3,5-二甲基苯酚 在 吡啶 、 copper(l) iodide 、 potassium tert-butylate 作用下， 反应 2.0h， 以42%的产率得到2-(3,5-Dimethylphenoxy)-4-chlor-pyridin
  参考文献：
  名称：

  THERAPEUTIC COMPOUNDS AND METHODS OF USE THEREOF

  摘要：

  该发明提供了一个式I的化合物：或其盐，其中R1、R2、R3、A、B、D、E、F和G的取值可在规范中描述，以及包含式I的化合物的组合物。这些化合物可用作溴结构域抑制剂。

  公开号：

  US20200377474A1