Piperazine, 1-acetyl-4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-, rel- | 67915-35-9

• 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: Piperazine, 1-acetyl-4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-, rel-
• 英文别名: 1-[4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazin-1-yl]ethanone
• CAS: 67915-35-9
• 化学式: C₂₅H₂₇Cl₂N₅O₄
• 分子量: 532.426
• InChiKey: LPIRMWRACFHEQI-DHLKQENFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  82
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  Piperazine, 1-acetyl-4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-, rel- 在 palladium on activated charcoal 噻吩 、 吡啶 、 sodium hydroxide 、 氢气 、 potassium carbonate 、 一水合肼 作用下， 以 1,4-二氧六环 、 甲醇 、 氯仿 、 乙二醇甲醚 、 二甲基亚砜 、 正丁醇 为溶剂， 反应 6.0h， 生成 伊曲康唑杂质20
  参考文献：
  名称：

  Antimycotic azoles. 7. Synthesis and antifungal properties of a series of novel triazol-3-ones

  摘要：

  A series of novel triazol-3-ones have been synthesized, and their in vitro and in vivo antifungal properties are reported. Compound 68 (itraconazole), which displays a pronounced oral activity against vaginal candidosis in rats and against microsporosis in guinea pigs, has been selected for clinical evaluation.

  DOI：

  10.1021/jm00373a015
• 作为产物：
  描述：

  1-(2,4-二氯l苯基)-2-(1H-1,2,4-噻唑-1-基)-乙酮 在 三氟甲磺酸 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 75.0h， 生成 Piperazine, 1-acetyl-4-[4-[[(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]-, rel-
  参考文献：
  名称：

  Total synthesis of (2R,4S,2′S,3′R)-hydroxyitraconazole: implementations of a recycle protocol and a mild and safe phase-transfer reagent for preparation of the key chiral units

  摘要：

  A convergent total synthesis of enantiomerically-pure (2R,4S,2'S,3'R)-hydroxyitraconazole 1b is described. The left dioxolane portion of the molecule was prepared in good yield by the conversion of (S)-10 to the corresponding enantiomerically and diastereomerically-pure acetonide (2R,4R)-3 by a recycle protocol involving diastereoselective crystallization of the tosylate salt, followed by re-equilibration of the mother liquor and crystallization. The right-hand triazolone moeity (2S,3R)-4 was generated by alkyaltion of triazolone 6 with enantiomerically pure cyclic sulfate (4R,5R)-7 under mild and essentially non-hazardous reaction conditions (TDA-1, K2CO3, acetonitrile). (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2003.01.001

文献信息

• 一种伊曲康唑衍生物的制备方法
  申请人：梯尔希(南京)药物研发有限公司

  公开号：CN108329304B

  公开（公告）日：2020-12-08

  本发明公开了一种伊曲康唑衍生物的制备方法，本发明以1‑乙酰‑4‑(4‑羟基苯基)哌嗪为原料，通过六步反应，实现伊曲康唑衍生物的合成。本发明提供的制备方法，工艺设计合理，可操作性强，反应条件比较温和，产率高，可实现工业化生产。本发明制备得到的伊曲康唑衍生物，可为伊曲康唑质量、安全性和效能科学评价提供重要依据，并且伊曲康唑衍生物药理活性好，可开发用于治疗各种原因引起的真菌感染的药物，具有重要的应用价值。
• Pd-catalyzed aminations of aryl triazolones: Effective synthesis of hydroxyitraconazole enantiomers
  作者：Gerald J. Tanoury、Chris H. Senanayake、Robert Hett、Amy M. Kuhn、Donald W. Kessler、Stephen A. Wald

  DOI：10.1016/s0040-4039(98)01493-2

  日期：1998.9

  A palladium-catalyzed amination of triazolone 3 by piperazine 2 was used as the key step in an efficient synthesis of highly enantiomerically-pure hydroxyitraconazole isomers. Compound 2 (>99%ee) was prepared by reaction of an achiral phenol precursor with the corresponding dioxolyl tosylate (>99% ee), and 3 was made by alkylation of 6 with 7 (>99%ee). (C) 1998 Elsevier Science Ltd. All rights reserved.
• Synthesis of novel water soluble benzylazolium prodrugs of lipophilic azole antifungals
  作者：Jun Ohwada、Chikako Murasaki、Toshikazu Yamazaki、Shigeyasu Ichihara、Isao Umeda、Nobuo Shimma

  DOI：10.1016/s0960-894x(02)00557-7

  日期：2002.10

  Water soluble N-benzyltriazolium or N-benzylimidazolium salt type prodrugs of several highly lipophilic triazole or imidazole antifungals have been synthesized. They were designed to undergo an enzymatic activation followed by a self-cleavage to release a parent drug. The prodrugs such as 16 had enough chemical stability and water solubility for parenteral use and were rapidly and quantitatively converted to the active substance in human plasma. (C) 2002 Elsevier Science Ltd. All rights reserved.
• HEERES, J.;BACKX, L. J. J.;MOSTMANS, J. H.
  作者：HEERES, J.、BACKX, L. J. J.、MOSTMANS, J. H.

  DOI：——

  日期：——
• TOPICAL TERBINAFINE FORMULATIONS AND METHODS OF ADMINISTERING SAME FOR THE TREATMENT OF FUNGAL INFECTIONS
  申请人：Cevc Gregor

  公开号：US20100104633A1

  公开（公告）日：2010-04-29

  The present invention relates to topical antifungal formulations terbinafine or a pharmaceutically acceptable salt thereof, a lipid, and a surfactant, and uses thereof for the treatment of skin and nail fungal infections.