4-azido-O-tritylbutahydroxamate | 1373219-29-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: 4-azido-O-tritylbutahydroxamate
• 英文别名: 4-azido-O-tritylbutylhydroxamate；4-azido-N-trityloxybutanamide
• CAS: 1373219-29-4
• 化学式: C₂₃H₂₂N₄O₂
• 分子量: 386.453
• InChiKey: JNTBXBKJXLDOCJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  52.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  4-azido-O-tritylbutahydroxamate 在 氯化铵 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三苯基膦 、 锌 、 四甲基胍 作用下， 以 四氢呋喃 、 乙醇 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.5h， 生成 (S)-tert-butyl 2-(4-(((2-amino-4-oxo-3,4-dihydropteridin-6-yl)methyl)amino)benzamido)-5-oxo-5-((4-oxo-4-((trityloxy)amino)butyl)amino)pentanoate
  参考文献：
  名称：

  Design and structure activity relationship of tumor-homing histone deacetylase inhibitors conjugated to folic and pteroic acids

  摘要：

  Histone deacetylase (HDAC) inhibition has recently emerged as a novel therapeutic approach for the treatment of various pathological conditions including cancer. Currently, two HDAC inhibitors (HDACi) - Vorinostat and Romidepsin - have been approved for the treatment of cutaneous T-cell lymphoma. However, HDACi remain ineffective against solid tumors and are associated with adverse events including cardiotoxicity. Targeted delivery may enhance the therapeutic indices of HDACi and enable them to be efficacious against solid tumors. We showed herein that morphing of folic and pteroic acids into the surface recognition group of HDACi results in hydroxamate and benzamide HDACi which derived tumor homing by targeting folate receptor (FR), a receptor commonly overexpressed in solid tumors. We observed a correlation between the potency of HDAC1 inhibition and cytotoxicity as only the potent pteroate hydroxamates, 11d and 11e, displayed antiproliferative activity against two representative FR-expression cancer cells. Our observation further supports the previous results which suggest that for a drug to be successfully targeted using the FR, it must be extremely potent against its primary target as the FR has a low delivery efficiency. Published by Elsevier Masson SAS.

  DOI：

  10.1016/j.ejmech.2015.04.014
• 作为产物：
  描述：

  4-叠氮丁酸 、 O-三苯甲基羟胺 在 O-(benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium tetrafluoroborate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 10.0h， 以91.2%的产率得到4-azido-O-tritylbutahydroxamate
  参考文献：
  名称：

  [EN] HISTONE DEACETYLASE (HDAC) INHIBITORS TARGETING PROSTATE TUMORS AND METHODS OF MAKING AND USING THEREOF
  [FR] INHIBITEURS D'HISTONE DÉSACÉTYLASE (HDAC) CIBLANT LES TUMEURS DE LA PROSTATE ET PROCÉDÉS POUR LES PRÉPARER ET LES UTILISER

  摘要：

  本文描述了Formula (I)的化合物及其制备和使用方法；其中AR是芳基基团，ZBG是锌结合基团，其他取代基如本文所定义。这些化合物可以作为药学上可接受的盐、前药或溶剂形式进行给药。这些化合物可能有助于治疗和/或预防可以包括激素敏感和激素耐药的前列腺癌等高增殖性疾病。这些化合物可以与药学上可接受的载体以及选择性地与一个或多个药学上可接受的赋形剂配制，用于肠道或静脉注射给药。

  公开号：

  WO2012050868A1

文献信息

• 具有AR和HDAC双重抑制作用的乙内酰脲类 和乙内酰硫脲类化合物及用途
  申请人：上海健康医学院

  公开号：CN109796437B

  公开（公告）日：2021-08-24

  本发明公开了一种具有AR和HDAC双重抑制作用的乙内酰脲类和乙内酰硫脲类化合物，其结构式如下所示：采用上述的化合物制备的药物具有抗前列腺癌的效果，为抗前列腺癌药物的研究提供了一个新方向，对开发抗前列腺癌药物具有重要意义。
• HISTONE DEACETYLASE (HDAC) INHIBITORS TARGETING PROSTATE TUMORS AND METHODS OF MAKING AND USING THEREOF
  申请人：Oyelere Adegboyega

  公开号：US20130289085A1

  公开（公告）日：2013-10-31

  Compounds of Formula (I), and methods of making and using thereof, are described herein; wherein AR is an aryl group, ZBG is a Zinc Binding Group, and other substituents are as defined herein. The compounds can be administered as a pharmaceutically acceptable salt, prodrug, or solvate. The compounds may be useful to treat and/or prevent hyperproliferative disorders which may include hormone sensitive and hormone refractory prostate cancers. The compounds can be formulated with a pharmaceutically acceptable carrier and, optionally one or more pharmaceutically acceptable excipients, for enteral or parenteral administration.

  本文介绍了化学式（I）的化合物及其制备和使用方法；其中AR是芳基基团，ZBG是锌结合基团，其他取代基的定义如本文所述。这些化合物可以作为药物可接受的盐、前药或溶剂形式进行给药。这些化合物可能有助于治疗和/或预防过度增殖性疾病，包括激素敏感和激素耐药的前列腺癌。这些化合物可以与药物可接受的载体和可选的一个或多个药物可接受的辅料一起制成口服或静脉给药制剂。
• Histone Deacetylase Inhibitors Equipped with Estrogen Receptor Modulation Activity
  作者：Berkley E. Gryder、Michael K. Rood、Kenyetta A. Johnson、Vishal Patil、Eric D. Raftery、Li-Pan D. Yao、Marcie Rice、Bahareh Azizi、Donald F. Doyle、Adegboyega K. Oyelere

  DOI：10.1021/jm400467w

  日期：2013.7.25

  We describe a set of novel histone deacetylase inhibitors (HDACi) equipped with either an antagonist or an agonist of the estrogen receptor (ER) to confer selective activity against breast cancers. These bifunctional compounds potently inhibit HDAC at nanomolar concentrations and either agonize or antagonize ER alpha and ER beta. The ER antagonist activities of tamoxifen-HDACi conjugates (Tam-HDACi) are nearly identical to those of tamoxifen. Conversely, ethynyl-estradiol-HDACi conjugates (EED-HDACi) have attenuated ER agonist activities relative to the parent ethynyl-estradiol. In silico docking analysis provides structural basis for the trends of ER agonism/antagonism and ER subtype selectivity. Excitingly, lead Tam-HDACi conjugates show anticancer activity that is selectively more potent against MCF-7 (ER alpha positive breast cancer) compared to MDA-MB-231 (triple negative breast cancer), DU145 (prostate cancer), or Vero (noncancerous cell line). This dual-targeting approach illustrates the utility of designing small molecules with an emphasis on cell-type selectivity, not merely improved potency, working toward a higher therapeutic index at the earliest stages of drug development.
• Dual-acting histone deacetylase-topoisomerase I inhibitors
  作者：William Guerrant、Vishal Patil、Joshua C. Canzoneri、Li-Pan Yao、Rebecca Hood、Adegboyega K. Oyelere

  DOI：10.1016/j.bmcl.2013.03.108

  日期：2013.6

  Current chemotherapy regimens are comprised mostly of single-target drugs which are often plagued by toxic side effects and resistance development. A pharmacological strategy for circumventing these drawbacks could involve designing multivalent ligands that can modulate multiple targets while avoiding the toxicity of a single-targeted agent. Two attractive targets, histone deacetylase (HDAC) and topoisomerase I (Topo I), are cellular modulators that can broadly arrest cancer proliferation through a range of downstream effects. Both are clinically validated targets with multiple inhibitors in therapeutic use. We describe herein the design and synthesis of dual-acting histone deacetylase-topoisomerase I inhibitors. We also show that these dual-acting agents retain activity against HDAC and Topo I, and potently arrest cancer proliferation. Published by Elsevier Ltd.
• US9139565B2
  申请人：——

  公开号：US9139565B2

  公开（公告）日：2015-09-22