(6-氯-吡啶-3-基)-哌啶-1-基-甲酮 | 6303-46-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: (6-氯-吡啶-3-基)-哌啶-1-基-甲酮
• 英文名称: (6-chloropyrimidin-4-yl)-(3,4-dichlorophenyl)-amine
• 英文别名: 6-chloro-N-(3,4-dichlorophenyl)pyrimidin-4-amine；4-chloro-6-(3,4-dichloroanilino)pyrimidine
• CAS: 6303-46-4
• 化学式: C₁₀H₆Cl₃N₃
• 分子量: 274.537
• InChiKey: DKFCSVINRQJSNI-UHFFFAOYSA-N

物化性质

• 沸点：
  400.4±45.0 °C(Predicted)
• 密度：
  1.544±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  37.8
• 氢给体数：
  1
• 氢受体数：
  3

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  (6-氯-吡啶-3-基)-哌啶-1-基-甲酮 在 (1,1'-bis(diphenylphosphino)ferrocene)palladium(II) dichloride 、 三乙胺 、 sodium hydroxide 作用下， 以 四氢呋喃 为溶剂， 20.0~50.0 ℃ 、500.01 kPa 条件下， 反应 34.0h， 生成 6-[(3,4-dichlorophenyl)amino]pyrimidine-4-carboxylic acid
  参考文献：
  名称：

  Development of a Series of Aryl Pyrimidine Kynurenine Monooxygenase Inhibitors as Potential Therapeutic Agents for the Treatment of Huntington’s Disease

  摘要：

  We report on the development of a series of pyrimidine carboxylic acids that are potent and selective inhibitors of kynurenine monooxygenase and competitive for kynurenine. We describe the SAR for this novel series and report on their inhibition of KMO activity in biochemical and cellular assays and their selectivity against other kynurenine pathway enzymes. We describe the optimization process that led to the identification of a program lead compound with a suitable ADME/PK profile for therapeutic development. We demonstrate that systemic inhibition of KMO in vivo with this lead compound provides pharmacodynamic evidence for modulation of kynurenine pathway metabolites both in the periphery and in the central nervous system.

  DOI：

  10.1021/jm501350y
• 作为产物：
  描述：

  4,6-二氯嘧啶 、 3,4-二氯苯胺 在 盐酸 作用下， 以 水 、 异丙醇 为溶剂， 反应 3.0h， 以77%的产率得到(6-氯-吡啶-3-基)-哌啶-1-基-甲酮
  参考文献：
  名称：

  结合或弯曲：通过基于 NMR 的构象分析区分变构 Abl 激酶激动剂和拮抗剂

  摘要：

  Bcr-Abl 的变构抑制剂已成为治疗 CML 的新治疗选择。使用基于片段的筛选，对与肉豆蔻酸口袋结合的新型 Abl 抑制剂进行了搜索。在这里，我们表明并非所有肉豆蔻酸酯配体都是功能抑制剂，但 C 端 helix_I 的构象状态是功能活性的结构决定因素。我们提出了一种基于 NMR 的构象分析来监测这个关键 helix_I 的构象，并表明弯曲 helix_I 的肉豆蔻酸配体是功能性拮抗剂，而与肉豆蔻酸口袋结合但不诱导这种构象变化的配体是激酶激动剂。变构激动剂对 c-Abl 的激活已在生化试验中得到证实。

  DOI：

  10.1021/ja101837n

文献信息

• Discovery of novel Bcr–Abl inhibitors targeting myristoyl pocket and ATP site
  作者：Jinyun Dong、Wen Lu、Xiaoyan Pan、Ping Su、Yaling Shi、Jinfeng Wang、Jie Zhang

  DOI：10.1016/j.bmc.2014.10.030

  日期：2014.12

  Bcr-Abl plays an essential role in the pathogenesis and development of chronic myeloid leukaemia (CML). Inhibition of Bcr-Abl has great potential for therapeutic intervention in CML. In order to obtain novel and potent Bcr-Abl inhibitors, twenty seven 4,6-disubstituted pyrimidines were synthesized and evaluated herein. The biological results indicated that four compounds of them (C4, C5, C16, and C23) were potent Bcr-Abl inhibitors which were comparable to positive control. Moreover, C4 and C5 displayed promising antiproliferative activity against K562 cells. The results suggested that these 4, 6-disubstituted pyrimidines could serve as promising leads for further optimization of Bcr-Abl inhibitors. (C) 2014 Elsevier Ltd. All rights reserved.