2-[(2R)-2-丁烷基]-4-{4-[4-(4-甲氧基苯基)-1-哌嗪基]苯基}-2,4-二氢-3H-1,2,4-三唑-3-酮 | 149809-44-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 中文名称: 2-[(2R)-2-丁烷基]-4-{4-[4-(4-甲氧基苯基)-1-哌嗪基]苯基}-2,4-二氢-3H-1,2,4-三唑-3-酮
• 英文名称: (R)-2-(sec-butyl)-4-(4-(4-(4-methoxyphenyl)piperazin-1-yl)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one
• 英文别名: R(-)-2,4-Dihydro-4-[4-[4-(4-methoxyphenyl)-1-piperazinyl]-phenyl]-2-(1-methylpropyl)-3H-1,2,4-triazole-3-one；2-sec-Butyl-4-(4-(4-(4-methoxyphenyl)piperazin-1-yl)phenyl)-2H-1,2,4-triazol-3(4H)-one, (R)-；2-[(2R)-butan-2-yl]-4-[4-[4-(4-methoxyphenyl)piperazin-1-yl]phenyl]-1,2,4-triazol-3-one
• CAS: 149809-44-9
• 化学式: C₂₃H₂₉N₅O₂
• 分子量: 407.516
• InChiKey: IVIVGYTUQVJVPF-GOSISDBHSA-N

物化性质

• 沸点：
  572.4±60.0 °C(Predicted)
• 密度：
  1.20±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  30
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  51.6
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-[(2R)-2-丁烷基]-4-{4-[4-(4-甲氧基苯基)-1-哌嗪基]苯基}-2,4-二氢-3H-1,2,4-三唑-3-酮 在 水 、 氢溴酸 、 caesium carbonate 作用下， 以 二甲基亚砜 、 甲苯 为溶剂， 反应 16.0h， 生成 itraconazole
  参考文献：
  名称：

  重新使用临床上有效的抗真菌药伊曲康唑作为抗癌化学疗法

  摘要：

  伊曲康唑（ITZ）是FDA批准的三唑类抗真菌药。最近的两次药物重新筛选将ITZ视为一种有前途的抗癌化学疗法，可抑制血管生成和刺猬（Hh）信号通路。我们已经合成并评估了第一代和第二代ITZ类似物的抗Hh和抗血管生成活性，以更全面地探究这些抗癌特性的结构要求。我们的总体结果表明，三唑功能是ITZ介导的血管生成抑制所必需的，但对于抑制Hh信号传导并不是必需的。立体化学定义的des的合成和评价-三唑ITZ类似物还提供有关ITZ支架二氧戊环环周围最佳构型的关键信息。最后，我们研究的结果表明，两种不同的细胞作用机制支配了ITZ支架的抗癌特性。

  DOI：

  10.1021/acs.jmedchem.5b01718
• 作为产物：
  描述：

  4-甲基苯磺酸 (S)-(+)-1-甲基丙酯 、 泊沙康唑-5 在 18-冠醚-6 、 potassium carbonate 作用下， 以 二甲基亚砜 为溶剂， 以73%的产率得到2-[(2R)-2-丁烷基]-4-{4-[4-(4-甲氧基苯基)-1-哌嗪基]苯基}-2,4-二氢-3H-1,2,4-三唑-3-酮
  参考文献：
  名称：

  Impact of Absolute Stereochemistry on the Antiangiogenic and Antifungal Activities of Itraconazole

  摘要：

  Itraconazole is used clinically as an antifungal agent and has recently been shown to possess antiangiogenic acitivity. Itraconazole has three chiral centers that give rise to eight stereoisomers. The complete role of stereochemistry in the two activities of itraconazole, however, has not been addressed adequately. For the first time, all eight stereoisomers of itraconazole (la h) have been synthesized and evaluated for activity against human endothelial cell proliferation and for antifungal activity against five fungal strains. Distinct antiangiogenic and antifungal activity profiles of the trans stereoisomers, especially 1e and If, suggest different molecular mechanisms underlying the antiangiogenic and antifungal activities of itraconazole.

  DOI：

  10.1021/ml1000068

文献信息

• ITRACONAZOLE AND SAPERCONAZOLE STEREOISOMERS
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：EP0631578A1

  公开（公告）日：1995-01-04
• [EN] ITRACONAZOLE AND SAPERCONAZOLE STEREOISOMERS
  申请人：JANSSEN PHARMACEUTICA N.V.

  公开号：WO1993019061A1

  公开（公告）日：1993-09-30

  (EN) The present invention is concerned with the stereoisomeric forms of itraconazole (X=Cl) and saperconazole (X=F), which may be represented by formula (cis-(I)), and the pharmaceutically acceptable acid addition salt forms thereof, processes for preparing said stereoisomeric forms, the complexes thereof with cyclodextrin derivatives, pharmaceutical compositions comprising said complexes and methods of preparing said complexes and pharmaceutical compositions.(FR) La présente invention concerne les formes stéréo-isomériques de l'itraconazole (X=Cl) et du saperconazole (X=F) qui peuvent être représentées par la formule (cis-(I)) ainsi que leurs formes de sels d'addition d'acide pharmaceutiquement acceptables, leurs complexes avec les dérivés de la cyclodextrine, des compositions pharmaceutiques comprenant lesdits complexes et les procédés de préparation de ces complexes et des compositions pharmaceutiques.
• Repurposing the Clinically Efficacious Antifungal Agent Itraconazole as an Anticancer Chemotherapeutic
  作者：Jennifer R. Pace、Albert M. DeBerardinis、Vibhavari Sail、Silvia K. Tacheva-Grigorova、Kelly A. Chan、Raymond Tran、Daniel S. Raccuia、Robert J. Wechsler-Reya、M. Kyle Hadden

  DOI：10.1021/acs.jmedchem.5b01718

  日期：2016.4.28

  suggest that the triazole functionality is required for ITZ-mediated inhibition of angiogenesis but that it is not essential for inhibition of Hh signaling. The synthesis and evaluation of stereochemically defined des-triazole ITZ analogues also provides key information as to the optimal configuration around the dioxolane ring of the ITZ scaffold. Finally, the results from our studies suggest that two

  伊曲康唑（ITZ）是FDA批准的三唑类抗真菌药。最近的两次药物重新筛选将ITZ视为一种有前途的抗癌化学疗法，可抑制血管生成和刺猬（Hh）信号通路。我们已经合成并评估了第一代和第二代ITZ类似物的抗Hh和抗血管生成活性，以更全面地探究这些抗癌特性的结构要求。我们的总体结果表明，三唑功能是ITZ介导的血管生成抑制所必需的，但对于抑制Hh信号传导并不是必需的。立体化学定义的des的合成和评价-三唑ITZ类似物还提供有关ITZ支架二氧戊环环周围最佳构型的关键信息。最后，我们研究的结果表明，两种不同的细胞作用机制支配了ITZ支架的抗癌特性。
• Impact of Absolute Stereochemistry on the Antiangiogenic and Antifungal Activities of Itraconazole
  作者：Wei Shi、Benjamin A. Nacev、Shridhar Bhat、Jun O. Liu

  DOI：10.1021/ml1000068

  日期：2010.7.8

  Itraconazole is used clinically as an antifungal agent and has recently been shown to possess antiangiogenic acitivity. Itraconazole has three chiral centers that give rise to eight stereoisomers. The complete role of stereochemistry in the two activities of itraconazole, however, has not been addressed adequately. For the first time, all eight stereoisomers of itraconazole (la h) have been synthesized and evaluated for activity against human endothelial cell proliferation and for antifungal activity against five fungal strains. Distinct antiangiogenic and antifungal activity profiles of the trans stereoisomers, especially 1e and If, suggest different molecular mechanisms underlying the antiangiogenic and antifungal activities of itraconazole.