(2S,4R)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-4-tozyloxymethyl-1,3-dioxolane

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S,4R)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-4-tozyloxymethyl-1,3-dioxolane
• 英文别名: [(2S,4R)-2-(2,4-dichlorophenyl)-2-(1,2,4-triazol-1-ylmethyl)-1,3-dioxolan-4-yl]methyl 4-methylbenzenesulfonate
• 化学式: C₂₀H₁₉Cl₂N₃O₅S
• 分子量: 484.36
• InChiKey: USLNGHIZGCHFQQ-OXQOHEQNSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  101
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-2-(sec-butyl)-4-(4-(4-(4-hydroxyphenyl)piperazin-1-yl)phenyl)-2,4-dihydro-3H-1,2,4-triazol-3-one 、 (2S,4R)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-4-tozyloxymethyl-1,3-dioxolane 在 sodium hydride 作用下， 以 二甲基亚砜 为溶剂， 以62%的产率得到(2S,4S,2'S)-Itraconazole
  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
• 作为产物：
  描述：

  (R)-(-)-对甲基苯磺酸-2,2-二甲基-1,3-二氧戊环基-4-甲酯 在 盐酸 、 三氟甲磺酸 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 66.0h， 生成 Toluene-4-sulfonic acid (2R,4R)-2-(2,4-dichloro-phenyl)-2-[1,2,4]triazol-1-ylmethyl-[1,3]dioxolan-4-ylmethyl ester 、 (2S,4R)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-4-tozyloxymethyl-1,3-dioxolane
  参考文献：
  名称：

  油菜甾醇类生物合成抑制剂YCZ - 2013的不对称合成及其绝对立体化学的影响。

  摘要：

  2 RS，4 RS -1-[[2-（2,4-二氯苯基）-4-（2-（2-丙烯氧基）苯氧基甲基）-1,3-二氧戊环-2-基]甲基]-的四个立体异构体制备了新型油菜素类固醇生物合成抑制剂1 H -1,2,4-三唑（YCZ - 2013）。通过使用相应的旋光纯R和S甲苯-4-磺酸2,3-二羟丙酯（R - 4，S - 4）制备2 RS，4 R - 5和2 RS，4 S - 5的非对映异构体）。通过对甲苯磺酸盐的非对映选择性结晶，然后用母液再平衡和色谱法，获得对映体和非对映体纯的丙酮化物（5）。通过手性高效液相色谱（HPLC）和NMR证实了四种目标化合物（YCZ - 2013）的光学纯度。这些立体异构体对拟南芥茎伸长的影响表明2 S，4 R - YCZ - 2013和2 R，4 S - YCZ - 2013的顺式异构体表现出强大的抑制活性，IC 50值分别约为24±3和24±2 nM。2 S，4 S

  DOI：

  10.1016/j.bmcl.2013.09.056

文献信息

• [EN] ITRACONAZOLE ANALOGS AND USE THEREOF<br/>[FR] ANALOGUES D'ITRACONAZOLE ET LEUR UTILISATION
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2013036866A1

  公开（公告）日：2013-03-14

  Provided herein are Itraconazole analogs. Also provided herein are methods of inhibition of Hedgehog pathway, vascular endothelial growth factor receptor 2 (VEGFR2) glycosylation, angiogenesis and treatment of disease with Itraconazole analogs.

  本文提供伊曲康唑类似物。本文还提供了使用伊曲康唑类似物抑制Hedgehog通路、血管内皮生长因子受体2（VEGFR2）的糖基化、血管生成以及治疗疾病的方法。
• CHIRALLY PURE ISOMERS OF ITRACONAZOLE FOR USE AS ANGIOGENESIS INHIBITORS
  申请人：Liu Jun O.

  公开号：US20130102614A1

  公开（公告）日：2013-04-25

  Described herein are methods of inhibiting angiogenesis, and treating and preventing disorders associated with angiogenesis by administering anti-angiogenesis compounds to a subject.

  本文描述了通过向受试者施用抗血管生成化合物来抑制血管生成并治疗和预防与血管生成相关的疾病的方法。
• 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
  作者：Gerald J. Tanoury、Robert Hett、H.Scott Wilkinson、Stephen A. Wald、Chris H. Senanayake

  DOI：10.1016/j.tetasy.2003.01.001

  日期：2003.11

  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.
• US9095589B2
  申请人：——

  公开号：US9095589B2

  公开（公告）日：2015-08-04
• 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.