[2-(3-Methoxypropoxy)-6-(trifluoromethyl)pyridin-3-yl]methanamine | 1444005-81-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: [2-(3-Methoxypropoxy)-6-(trifluoromethyl)pyridin-3-yl]methanamine
• 英文别名: [2-(3-methoxypropoxy)-6-(trifluoromethyl)pyridin-3-yl]methanamine
• CAS: 1444005-81-5
• 化学式: C₁₁H₁₅F₃N₂O₂
• 分子量: 264.248
• InChiKey: OAKDEWNVKMOMCQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  18
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  57.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-氯-6-三氟甲基烟腈 在 dimethyl sulfide borane 、 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 13.0h， 生成 [2-(3-Methoxypropoxy)-6-(trifluoromethyl)pyridin-3-yl]methanamine
  参考文献：
  名称：

  2-(3-Fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists: Structure activity relationships of the 2-oxy pyridine C-region

  摘要：

  The structure activity relationships of 2-oxy pyridine derivatives in the C-region of N-(6-trifluoromethylpyridin-3-ylmethyl) 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as hTRPV1 antagonists were investigated. The analysis indicated that the lipophilicity of the 2-oxy substituents was critical for potent antagonism and 4 or 5 carbons appeared to be optimal for activity. Multiple compounds proved to have comparable activity to 1, which had been reported as the most potent antagonist for capsaicin activity among the previous series of compounds. Further analysis of compounds 22 (2-isobutyloxy) and 53 (2-benzyloxy) in the formalin test in mice demonstrated strong analgesic activity with full efficacy. Docking analysis of 535 using our hTRPV1 homology model indicated that the A- and B-region 2-(3fluoro-4-methylsulfonylaminophenyl)propanamide made important hydrophobic and hydrogen bonding interactions with Tyr511 and that the C-region 6-trifluoromethyl and 2-benzyloxy groups of pyridine occupied the two hydrophobic binding pockets, respectively. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.003

文献信息

• 2-(3-Fluoro-4-methylsulfonylaminophenyl)propanamides as potent TRPV1 antagonists: Structure activity relationships of the 2-oxy pyridine C-region
  作者：Shivaji A. Thorat、Dong Wook Kang、HyungChul Ryu、Myeong Seop Kim、Ho Shin Kim、Jihyae Ann、Taehwan Ha、Sung-Eun Kim、Karam Son、Sun Choi、Peter M. Blumberg、Robert Frank、Gregor Bahrenberg、Klaus Schiene、Thomas Christoph、Jeewoo Lee

  DOI：10.1016/j.ejmech.2013.04.003

  日期：2013.6

  The structure activity relationships of 2-oxy pyridine derivatives in the C-region of N-(6-trifluoromethylpyridin-3-ylmethyl) 2-(3-fluoro-4-methylsulfonylaminophenyl)propanamides as hTRPV1 antagonists were investigated. The analysis indicated that the lipophilicity of the 2-oxy substituents was critical for potent antagonism and 4 or 5 carbons appeared to be optimal for activity. Multiple compounds proved to have comparable activity to 1, which had been reported as the most potent antagonist for capsaicin activity among the previous series of compounds. Further analysis of compounds 22 (2-isobutyloxy) and 53 (2-benzyloxy) in the formalin test in mice demonstrated strong analgesic activity with full efficacy. Docking analysis of 535 using our hTRPV1 homology model indicated that the A- and B-region 2-(3fluoro-4-methylsulfonylaminophenyl)propanamide made important hydrophobic and hydrogen bonding interactions with Tyr511 and that the C-region 6-trifluoromethyl and 2-benzyloxy groups of pyridine occupied the two hydrophobic binding pockets, respectively. (C) 2013 Elsevier Masson SAS. All rights reserved.