(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-methylphenyl)-6-(3-methylpiperazin-l-yl)pyridin-3-yl]-N-methylisobutyramide | 1379446-14-6

• 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: (S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-methylphenyl)-6-(3-methylpiperazin-l-yl)pyridin-3-yl]-N-methylisobutyramide
• CAS: 1379446-14-6
• 化学式: C₃₀H₃₁F₇N₄O
• 分子量: 596.591
• InChiKey: LFARTFDQTOKRKJ-SFHVURJKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.97
• 重原子数：
  42.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  48.47
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-methylphenyl)-6-(3-methylpiperazin-l-yl)pyridin-3-yl]-N-methylisobutyramide 、 甲基磺酰氯 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 以75%的产率得到RO4908594
  参考文献：
  名称：

  Identification of a Crucial Amino Acid in the Helix Position 6.51 of Human Tachykinin Neurokinin 1 and 3 Receptors Contributing to the Insurmountable Mode of Antagonism by Dual NK₁/NK₃ Antagonists

  摘要：

  The neurokinins are neuropeptides that elicit their effect through three GPCRs called NK1, NK2, and NK3. Compounds 5 and 6 are dual hNK(1) (K-1 of 0.7 and 0.3 nM) and hNK(3) (K-1 of 2.9 and 1.7 nM) antagonists. Both compounds exhibit an insurmountable mode of antagonism at hNK(1), whereas at hNK(3), they differ in that 5 is an insurmountable but 6 a surmountable antagonist. Using homology modeling and site-directed mutagenesis, hNK(1)-Phe264 and hNK(3)-Tyr315 were found to be the molecular determinants of hNK(1) and hNK(3) antagonism by 5 and 6. In [H-3]IP studies, the mutation hNK(1)-F264Y converted the mode of action of 5 from insurmountable to partial insurmountable antagonism while it had no effect on that of 6. Conversely, the mutation hNK(3)-Y315F enhanced the insurmountable behavior of 5 and converted 6's surmountable to an insurmountable antagonism. This finding was further confirmed by characterizing additional derivatives of 5 and 6, most notably with a hybrid structure.

  DOI：

  10.1021/jm2017072
• 作为产物：
  描述：

  2-(3,5-bis-trifluoromethylphenyl)-N-[6-chloro-4-(4-fluoro-2-methylphenyl)pyridin-3-yl]-N-methyl isobutyramide 、 (S)-(+)-2-甲基哌嗪 在 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 反应 0.5h， 以51%的产率得到(S)-2-(3,5-bis(trifluoromethyl)phenyl)-N-[4-(4-fluoro-2-methylphenyl)-6-(3-methylpiperazin-l-yl)pyridin-3-yl]-N-methylisobutyramide
  参考文献：
  名称：

  Identification of a Crucial Amino Acid in the Helix Position 6.51 of Human Tachykinin Neurokinin 1 and 3 Receptors Contributing to the Insurmountable Mode of Antagonism by Dual NK₁/NK₃ Antagonists

  摘要：

  The neurokinins are neuropeptides that elicit their effect through three GPCRs called NK1, NK2, and NK3. Compounds 5 and 6 are dual hNK(1) (K-1 of 0.7 and 0.3 nM) and hNK(3) (K-1 of 2.9 and 1.7 nM) antagonists. Both compounds exhibit an insurmountable mode of antagonism at hNK(1), whereas at hNK(3), they differ in that 5 is an insurmountable but 6 a surmountable antagonist. Using homology modeling and site-directed mutagenesis, hNK(1)-Phe264 and hNK(3)-Tyr315 were found to be the molecular determinants of hNK(1) and hNK(3) antagonism by 5 and 6. In [H-3]IP studies, the mutation hNK(1)-F264Y converted the mode of action of 5 from insurmountable to partial insurmountable antagonism while it had no effect on that of 6. Conversely, the mutation hNK(3)-Y315F enhanced the insurmountable behavior of 5 and converted 6's surmountable to an insurmountable antagonism. This finding was further confirmed by characterizing additional derivatives of 5 and 6, most notably with a hybrid structure.

  DOI：

  10.1021/jm2017072