2-(4-Methylpiperazin-1-yl)-6-(trifluoromethyl)pyridine-3-carbonitrile

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: 2-(4-Methylpiperazin-1-yl)-6-(trifluoromethyl)pyridine-3-carbonitrile
• 化学式: C₁₂H₁₃F₃N₄
• 分子量: 270.257
• InChiKey: IEXWZTBSQMJWEJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  43.2
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2-(4-Methylpiperazin-1-yl)-6-(trifluoromethyl)pyridine-3-carbonitrile 在 盐酸 、 palladium 10% on activated carbon 、 氢气 作用下， 以 甲醇 、 水 为溶剂， 反应 6.0h， 生成 [2-(4-Methylpiperazin-1-yl)-6-(trifluoromethyl)pyridin-3-yl]methanamine
  参考文献：
  名称：

  2-(3-Fluoro-4-methylsulfonylaminophenyl)propanamides as Potent Transient Receptor Potential Vanilloid 1 (TRPV1) Antagonists: Structure–Activity Relationships of 2-Amino Derivatives in the N-(6-Trifluoromethylpyridin-3-ylmethyl) C-Region

  摘要：

  A series of N-(2-amino-6-trifluoromethylpyridin-3-ylmethyl)-2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides were designed combining previously identified pharmacophoric elements and evaluated as hTRPV1 antagonists. The SAR analysis indicated that specific hydrophobic interactions of the 2-amino substituents in the C-region of the ligand were critical for high hTRPV1 binding potency. In particular, compound 49S was an excellent TRPV1 antagonist (K-i(CAP) = 0.2 nM; IC50(pH) = 6.3 nM) and was thus approximately 100- and 20-fold more potent, respectively, than the parent compounds 2 and 3 for capsaicin antagonism. Furthermore, it demonstrated strong analgesic activity in the rat neuropathic model superior to 2 with almost no side effects. Compound 49S antagonized capsaicin induced hypothermia in mice but showed TRPV1-related hyperthermia. The basis for the high potency of 49S compared to 2 is suggested by docking analysis with our hTRPV1 homology model in which the 4-methylpiperidinyl group in the C-region of 49S made additional hydrophobic interactions with the hydrophobic region.

  DOI：

  10.1021/jm300780p
• 作为产物：
  描述：

  (E,2Z)-2-[amino-(4-methylpiperazin-1-yl)methylidene]-6,6,6-trifluoro-5-oxohex-3-enenitrile 以 乙腈 为溶剂， 反应 1.0h， 以100%的产率得到2-(4-Methylpiperazin-1-yl)-6-(trifluoromethyl)pyridine-3-carbonitrile
  参考文献：
  名称：

  Cocco, Maria Teresa; Congiu, Cenzo; Onnis, Valentina, Journal of Heterocyclic Chemistry, 1995, vol. 32, # 2, p. 543 - 546

  摘要：

  DOI：