2-chloro-4,6-bis(4'-chlorophenethylamino)-1,3,5-triazine | 85196-48-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三嗪类
• 英文名称: 2-chloro-4,6-bis(4'-chlorophenethylamino)-1,3,5-triazine
• CAS: 85196-48-1
• 化学式: C₁₉H₁₈Cl₃N₅
• 分子量: 422.744
• InChiKey: KEKKDDGMLMDBHX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.14
• 重原子数：
  27.0
• 可旋转键数：
  8.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  62.73
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  1-氨基-4-甲基哌嗪 、 2-chloro-4,6-bis(4'-chlorophenethylamino)-1,3,5-triazine 以 四氢呋喃 为溶剂， 反应 0.33h， 以55%的产率得到2,4-bis(4'-chlorophenethylamino)-6-(4'-methylpiperazin-1'-ylamino)-1,3,5-triazine
  参考文献：
  名称：

  Triazine-Based Vanilloid 1 Receptor Open Channel Blockers: Design, Synthesis, Evaluation, and SAR Analysis

  摘要：

  The thermosensory transient receptor potential vanilloid 1 channel (TRPV1) is a polymodal receptor activated by physical and chemical stimuli. TRPV1 activity is drastically potentiated by proinflammatory agents released upon tissue damage. Given the pivotal role of TRPV1 in human pain, there is pressing need for improved TRPV1 antagonists, the development of which will require identification of new pharmacophore scaffolds. Uncompetitive antagonists acting as open-channel blockers might serve as activity-dependent blockers that preferentially modulate the activity of overactive channels, thus displaying fewer side effects than their competitive counterparts. Herein we report the design, synthesis, biological evaluation, and SAR analysis of a family of triazine-based compounds acting as TRPV1 uncompetitive antagonists. We identified the triazine 8aA as a potent, pure antagonist that inhibits TRPV1 channel activity with nanomolar efficacy and strong voltage dependency. It represents a new class of activity-dependent TRPV1 antagonists and may serve as the basis for lead optimization in the development of new analgesics.

  DOI：

  10.1021/jm200981s
• 作为产物：
  描述：

  三聚氯氰 、 4-氯苯乙胺 以 四氢呋喃 为溶剂， 反应 0.17h， 以94%的产率得到2-chloro-4,6-bis(4'-chlorophenethylamino)-1,3,5-triazine
  参考文献：
  名称：

  Triazine-Based Vanilloid 1 Receptor Open Channel Blockers: Design, Synthesis, Evaluation, and SAR Analysis

  摘要：

  The thermosensory transient receptor potential vanilloid 1 channel (TRPV1) is a polymodal receptor activated by physical and chemical stimuli. TRPV1 activity is drastically potentiated by proinflammatory agents released upon tissue damage. Given the pivotal role of TRPV1 in human pain, there is pressing need for improved TRPV1 antagonists, the development of which will require identification of new pharmacophore scaffolds. Uncompetitive antagonists acting as open-channel blockers might serve as activity-dependent blockers that preferentially modulate the activity of overactive channels, thus displaying fewer side effects than their competitive counterparts. Herein we report the design, synthesis, biological evaluation, and SAR analysis of a family of triazine-based compounds acting as TRPV1 uncompetitive antagonists. We identified the triazine 8aA as a potent, pure antagonist that inhibits TRPV1 channel activity with nanomolar efficacy and strong voltage dependency. It represents a new class of activity-dependent TRPV1 antagonists and may serve as the basis for lead optimization in the development of new analgesics.

  DOI：

  10.1021/jm200981s