(S)-5-azido-6-(2,4,6-trifluorophenyl)-N-(1,1,1-trifluoropropan-2-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine | 1619924-31-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 三唑并嘧啶类
• 英文名称: (S)-5-azido-6-(2,4,6-trifluorophenyl)-N-(1,1,1-trifluoropropan-2-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
• 英文别名: 5-azido-6-(2,4,6-trifluorophenyl)-N-[(2S)-1,1,1-trifluoropropan-2-yl]-[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
• CAS: 1619924-31-0
• 化学式: C₁₄H₈F₆N₈
• 分子量: 402.262
• InChiKey: DFGRCRLQNKYQQJ-YFKPBYRVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  69.5
• 氢给体数：
  1
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  2,4,6-三氟苯基丙二酸二乙酯 在 sodium azide 、 三正丁胺 、 N,N-二异丙基乙胺 、 sodium hydroxide 、 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 32.0h， 生成 (S)-5-azido-6-(2,4,6-trifluorophenyl)-N-(1,1,1-trifluoropropan-2-yl)[1,2,4]triazolo[1,5-a]pyrimidin-7-amine
  参考文献：
  名称：

  Brain-Penetrant, Orally Bioavailable Microtubule-Stabilizing Small Molecules Are Potential Candidate Therapeutics for Alzheimer’s Disease and Related Tauopathies

  摘要：

  Microtubule (MT) stabilizing drugs hold promise as potential treatments for Alzheimer's disease (AD) and related tauopathies. However, thus far epothilone D has been the only brain-penetrant MT-stabilizer to be evaluated in tau transgenic mice and in AD patients. Furthermore, this natural product exhibits potential deficiencies as a drug candidate, including an intravenous route of administration and the inhibition of the P-glycoprotein (Pgp) transporter. Thus, the identification of alternative CNS-active MT-stabilizing agents that lack these potential limitations is of interest. Toward this objective, we have evaluated representative compounds from known classes of non-naturally occurring MT-stabilizing small molecules. This led to the identification of selected triazolopyrimidines and phenylpyrimidines that are orally bioavailable and brain-penetrant without disruption of Pgp function. Pharmacodynamic studies confirmed that representative compounds from these series enhance MT-stabilization in the brains of wild-type mice. Thus, these classes of MT-stabilizers hold promise for the development of orally active, CNS-directed MT-stabilizing therapies.

  DOI：

  10.1021/jm5005623

文献信息

• Brain-Penetrant, Orally Bioavailable Microtubule-Stabilizing Small Molecules Are Potential Candidate Therapeutics for Alzheimer’s Disease and Related Tauopathies
  作者：Kevin Lou、Yuemang Yao、Adam T. Hoye、Michael J. James、Anne-Sophie Cornec、Edward Hyde、Bryant Gay、Virginia M.-Y. Lee、John Q. Trojanowski、Amos B. Smith、Kurt R. Brunden、Carlo Ballatore

  DOI：10.1021/jm5005623

  日期：2014.7.24

  Microtubule (MT) stabilizing drugs hold promise as potential treatments for Alzheimer's disease (AD) and related tauopathies. However, thus far epothilone D has been the only brain-penetrant MT-stabilizer to be evaluated in tau transgenic mice and in AD patients. Furthermore, this natural product exhibits potential deficiencies as a drug candidate, including an intravenous route of administration and the inhibition of the P-glycoprotein (Pgp) transporter. Thus, the identification of alternative CNS-active MT-stabilizing agents that lack these potential limitations is of interest. Toward this objective, we have evaluated representative compounds from known classes of non-naturally occurring MT-stabilizing small molecules. This led to the identification of selected triazolopyrimidines and phenylpyrimidines that are orally bioavailable and brain-penetrant without disruption of Pgp function. Pharmacodynamic studies confirmed that representative compounds from these series enhance MT-stabilization in the brains of wild-type mice. Thus, these classes of MT-stabilizers hold promise for the development of orally active, CNS-directed MT-stabilizing therapies.