1,5-bis(4-methoxyphenyl)-3-(2,2,2-trifluoroethoxy)-1H-1,2,4-triazole | 524699-85-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1,5-bis(4-methoxyphenyl)-3-(2,2,2-trifluoroethoxy)-1H-1,2,4-triazole
• 英文别名: 1,5-bis(4-methoxyphenyl)-3-(2,2,2-trifluoroethoxy)-1,2,4-triazole
• CAS: 524699-85-2
• 化学式: C₁₈H₁₆F₃N₃O₃
• 分子量: 379.339
• InChiKey: YBEGHAAVDAFSSE-UHFFFAOYSA-N

物化性质

• 沸点：
  485.4±55.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  27
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  58.4
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1,5-bis(4-methoxyphenyl)-3-(2,2,2-trifluoroethoxy)-1H-1,2,4-triazole 在 正丁基锂 、 potassium carbonate 、 氯化铵 、 4,7,13,16,21,24-六氧-1,10-二氮双环[8.8.8]二十六烷 、 氢氟酸 作用下， 以 四氢呋喃 、 水 、 二甲基亚砜 为溶剂， 反应 1.08h， 生成 [¹⁸F]PS13
  参考文献：
  名称：

  [18F]PS13 的合成及其作为 PET 放射性配体在猴体内的 Cyclooxygenase-1 的评价

  摘要：

  环氧合酶-1 (COX-1) 及其同工酶 COX-2 是合成前列腺素的关键酶。使用正电子发射断层扫描 (PET) 对 COX-1 和 COX-2 选择性放射性配体进行成像可以阐明这些酶如何参与炎症状况并有助于发现改进的抗炎药物。我们之前已经标记了选择性高亲和力 COX-1 配体 1,5-bis(4-methoxyphenyl)-3-(2,2,2-trifluoroethoxy)-1 H -1,2,4-triazole (PS13) , 含碳 11 ( t 1/2 = 20.4 分钟)。这种放射性配体 ([ 11 C]PS13) 已成功用于猴子和人脑以及外围的 COX-1 的 PET 成像。[ 11 C]PS13 正在临床研究中使用。用氟 18 替代 PS13 标记（t 1/2 = 109.8 分钟）是理想的，以提供一种寿命更长的高活性放射性配体，可以很容易地分布在成像中心之间。然而，在其 1

  DOI：

  10.1021/acschemneuro.0c00737
• 作为产物：
  描述：

  4-苯甲氧基苯(甲)酰氯 在 吡啶 、 三氯化硼 、 potassium carbonate 、 potassium iodide 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 46.6h， 生成 1,5-bis(4-methoxyphenyl)-3-(2,2,2-trifluoroethoxy)-1H-1,2,4-triazole
  参考文献：
  名称：

  3-Substituted 1,5-Diaryl-1H-1,2,4-triazoles as Prospective PET Radioligands for Imaging Brain COX-1 in Monkey. Part 1: Synthesis and Pharmacology

  摘要：

  Cyclooxygenase-1 (COX-1) is a key enzyme in the biosynthesis of proinflammatory thromboxanes and prostaglandins and is found in glial and neuronal cells within brain. COX-1 expression is implicated in numerous neuroinflammatory states. We aim to find a direct-acting positron emission tomography (PET) radioligand for imaging COX-1 in human brain as a potential biomarker of neuroinflammation and for serving as a tool in drug development. Seventeen 3-substituted 1,5-diaryl-1H-1,2,4-triazoles were prepared as prospective COX-1 PET radioligands. From this set, three 1,5-(4-methoxypheny1)-1H-1,2,4-triazoles, carrying a 3-methoxy (5), 3-(1,1,1-trifluoroethoxy) (20), or 3-fluoromethoxy substituent (6), were selected for radioligand development, based mainly on their high affinities and selectivities for inhibiting human COX-1, absence of carboxyl group, moderate computed lipophilicities, and scope for radiolabeling with carbon-11 (t(1/2) = 20.4 min) or fluorine-18 (t(1/2) = 109.8 min). Methods were developed for producing [C-11]5, [C-11]20, and [d(2)-F-18]6 from hydroxy precursors in a form ready for intravenous injection for prospective evaluation in monkey with PET.

  DOI：

  10.1021/acschemneuro.8b00102

文献信息

• Triazole derivatives
  申请人：——

  公开号：US20030191155A1

  公开（公告）日：2003-10-09

  A compound of the formula (I): 1 wherein R 1 is lower alkyl which is optionally substituted with halogen, cyano, N,N-di(lower)alkylcarbamoyl, phenyl optionally substituted with halogen, or heterocyclic group, cyclo(lower)alkyl, lower alkynyl, or N,N-di(lower)alkylcarbamoyl; R 2 is lower alkyl, lower alkoxy, cyano, or 1H-pyrrol-1-yl; R 3 is lower alkyl, lower alkoxy, or cyano; X is O, S, SO or SO 2 ; Y and Z are each CH or N; and m is 0 or 1; or salts thereof, which are useful as a medicament.

  一种化合物的分子式为(I):1其中R1是低碳烷基，可以选择性地用卤素、氰基、N,N-二(低碳)氨基甲酰基、苯基（可以选择性地用卤素取代）、或杂环基、环(低碳)烷基、低碳炔基或N,N-二(低碳)氨基甲酰基取代；R2是低碳烷基、低碳氧基、氰基或1H-吡咯-1-基；R3是低碳烷基、低碳氧基或氰基；X是氧、硫、亚砜或亚砜二；Y和Z分别是CH或N；m为0或1；或其盐，可用作药物。
• SOLID DISPERSION COMPRISING TRIAZOLE COMPOUND
  申请人：Astellas Pharma Inc.

  公开号：EP2581084A1

  公开（公告）日：2013-04-17

  A solid dispersion comprising a poorly soluble pharmaceutical compound, such as 3-methoxy-1,5-bis(4-methoxyphenyl)- 1H-1,2,4-triazole, which has excellent ease of handling and stability is provided. The solid dispersion comprises a polymeric carrier (for example, a polymer selected from a group consisting of polyvinylpyrrolidone and copolyvidone) and further comprising hydroxypropyl methylcellulose as desired.

  本发明提供了一种固体分散体，它包含一种溶解性较差的药物化合物，如 3-甲氧基-1,5-双（4-甲氧基苯基）-1H-1,2,4-三唑，具有极佳的易操作性和稳定性。固体分散体包括聚合物载体（例如，选自聚乙烯吡咯烷酮和共聚维酮组成的聚合物），并根据需要进一步包括羟丙基甲基纤维素。
• US6927230B2
  申请人：——

  公开号：US6927230B2

  公开（公告）日：2005-08-09
• 3-Substituted 1,5-Diaryl-1<i>H</i>-1,2,4-triazoles as Prospective PET Radioligands for Imaging Brain COX-1 in Monkey. Part 1: Synthesis and Pharmacology
  作者：Prachi Singh、Stal Shrestha、Michelle Y. Cortes-Salva、Kimberly J. Jenko、Sami S. Zoghbi、Cheryl L. Morse、Robert B. Innis、Victor W. Pike

  DOI：10.1021/acschemneuro.8b00102

  日期：2018.11.21

  Cyclooxygenase-1 (COX-1) is a key enzyme in the biosynthesis of proinflammatory thromboxanes and prostaglandins and is found in glial and neuronal cells within brain. COX-1 expression is implicated in numerous neuroinflammatory states. We aim to find a direct-acting positron emission tomography (PET) radioligand for imaging COX-1 in human brain as a potential biomarker of neuroinflammation and for serving as a tool in drug development. Seventeen 3-substituted 1,5-diaryl-1H-1,2,4-triazoles were prepared as prospective COX-1 PET radioligands. From this set, three 1,5-(4-methoxypheny1)-1H-1,2,4-triazoles, carrying a 3-methoxy (5), 3-(1,1,1-trifluoroethoxy) (20), or 3-fluoromethoxy substituent (6), were selected for radioligand development, based mainly on their high affinities and selectivities for inhibiting human COX-1, absence of carboxyl group, moderate computed lipophilicities, and scope for radiolabeling with carbon-11 (t(1/2) = 20.4 min) or fluorine-18 (t(1/2) = 109.8 min). Methods were developed for producing [C-11]5, [C-11]20, and [d(2)-F-18]6 from hydroxy precursors in a form ready for intravenous injection for prospective evaluation in monkey with PET.
• Synthesis of [¹⁸F]PS13 and Evaluation as a PET Radioligand for Cyclooxygenase-1 in Monkey
  作者：Carlotta Taddei、Cheryl L. Morse、Min-Jeong Kim、Jeih-San Liow、Jose Montero Santamaria、Andrea Zhang、Lester S. Manly、Paolo Zanotti-Fregonara、Robert L. Gladding、Sami S. Zoghbi、Robert B. Innis、Victor W. Pike

  DOI：10.1021/acschemneuro.0c00737

  日期：2021.2.3

  cyclotron-produced [18F]fluoride ion to gem-difluorovinyl precursors, either to label PS13 in one step or to produce [18F]2,2,2-trifluoroethyl p-toluenesulfonate for labeling a hydroxyl precursor. From the latter two-step approach, we obtained [18F]PS13 ready for intravenous injection in a decay-corrected radiochemical yield of 7.9% and with a molar activity of up to 7.9 GBq/μmol. PET imaging of monkey

  环氧合酶-1 (COX-1) 及其同工酶 COX-2 是合成前列腺素的关键酶。使用正电子发射断层扫描 (PET) 对 COX-1 和 COX-2 选择性放射性配体进行成像可以阐明这些酶如何参与炎症状况并有助于发现改进的抗炎药物。我们之前已经标记了选择性高亲和力 COX-1 配体 1,5-bis(4-methoxyphenyl)-3-(2,2,2-trifluoroethoxy)-1 H -1,2,4-triazole (PS13) , 含碳 11 ( t 1/2 = 20.4 分钟)。这种放射性配体 ([ 11 C]PS13) 已成功用于猴子和人脑以及外围的 COX-1 的 PET 成像。[ 11 C]PS13 正在临床研究中使用。用氟 18 替代 PS13 标记（t 1/2 = 109.8 分钟）是理想的，以提供一种寿命更长的高活性放射性配体，可以很容易地分布在成像中心之间。然而，在其 1