(E)-N-Hydroxy-3-[4-({(2-hydroxy-1-hydroxymethyl-ethyl)-[2-(1H-indol-3-yl)-ethyl]-amino}-methyl)-phenyl]-acrylamide | 404950-89-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (E)-N-Hydroxy-3-[4-({(2-hydroxy-1-hydroxymethyl-ethyl)-[2-(1H-indol-3-yl)-ethyl]-amino}-methyl)-phenyl]-acrylamide
• 英文别名: (2E)-N-Hydroxy-3-[4-[[[2-hydroxy-1-(hydroxymethyl)ethyl][2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide；(E)-3-[4-[[1,3-dihydroxypropan-2-yl-[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]-N-hydroxyprop-2-enamide
• CAS: 404950-89-6
• 化学式: C₂₃H₂₇N₃O₄
• 分子量: 409.485
• InChiKey: IQIQQDNFMRPMIO-MDZDMXLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  30
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  109
• 氢给体数：
  5
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (2E)-3-[4-[[[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenoic acid methyl ester 在 sodium hydroxide 、 羟胺 、 sodium cyanoborohydride 作用下， 以 甲醇 为溶剂， 生成 (E)-N-Hydroxy-3-[4-({(2-hydroxy-1-hydroxymethyl-ethyl)-[2-(1H-indol-3-yl)-ethyl]-amino}-methyl)-phenyl]-acrylamide
  参考文献：
  名称：

  N-Hydroxy-3-phenyl-2-propenamides as Novel Inhibitors of Human Histone Deacetylase with in Vivo Antitumor Activity:  Discovery of (2E)-N-Hydroxy-3-[4-[[(2-hydroxyethyl)[2-(1H-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide (NVP-LAQ824)

  摘要：

  A series of N-hydroxy-3-phenyl-2-propenamides were prepared as novel inhibitors of human histone deacetylase (HDAC). These compounds were potent enzyme inhibitors, having IC(50)s < 400 nM in a partially purified enzyme assay. However, potency in cell growth inhibition assays ranged over 2 orders of magnitude in two human carcinoma cell lines. Selected compounds having cellular IC50 < 750 nM were tested for maximum tolerated dose (MTD) and for efficacy in the HCT116 human colon tumor xenograft assay. Four compounds having an MTD 100 mg/kg were selected for dose-response studies in the HCT116 xenograft model. One compound, 9 (NVP-LAQ824), had significant dose-related activity in the HCT116 colon and A549 lung tumor models, high MTD, and low gross toxicity. On the basis, in part, of these properties, 9 has entered human clinical trials in 2002.

  DOI：

  10.1021/jm030235w

文献信息

• Method of Use of Deacetylase Inhibitors
  申请人：Izumo Seigo

  公开号：US20090012066A1

  公开（公告）日：2009-01-08

  The present invention provides methods of treating and/or preventing pathologic cardiac hypertrophy and heart failure comprising administering hydroxamate compounds which are deacetylase inhibitors.

  本发明提供了一种治疗和/或预防病理性心肌肥大和心力衰竭的方法，包括给予去乙酰化酶抑制剂的羟肟酸化合物。
• DEACETYLASE INHIBITORS
  申请人：Remiszewski Stacy William

  公开号：US20080176849A1

  公开（公告）日：2008-07-24

  The present invention provides hydroxamate compounds which are deacetylase inhibitors. The compounds are suitable for pharmaceutical compositions having anti-proliferative properties.

  本发明提供了一种羟肟酸化合物，其为去乙酰化酶抑制剂。这些化合物适用于具有抗增殖性质的药物组合物。
• COMPOUNDS AND METHODS FOR IMPROVING IMPAIRED ENDOGENOUS FIBRINOLYSIS USING HISTONE DEACETYLASE INHIBITORS
  申请人：Larsson Pia

  公开号：US20140051716A1

  公开（公告）日：2014-02-20

  There is provided a compound which is a histone deacetylase (HDAC) inhibitor, or a pharmaceutically acceptable ester, amide, solvate or salt thereof, for use in: (I) treating or preventing a pathological condition associated with excess fibrin deposition and/or thrombus formation; and/or (II) potentiating the degradation of fibrin deposits and preventing such deposits associated with pathological conditions or which may lead to such conditions, wherein the HDAC inhibitor, and the dose thereof, is as described in the description. There is also provided valproic acid, or a pharmaceutically acceptable salt thereof, for use in improving or normalizing endogenous fibrinolysis impaired by local or systemic inflammation.
• [EN] METHOD OF USE OF DEACETYLASE INHIBITORS<br/>[FR] PROCEDE D'UTILISATION D'INHIBITEURS DE LA DESACETYLASE
  申请人：NOVARTIS AG

  公开号：WO2007021682A1

  公开（公告）日：2007-02-22

  [EN] The present invention provides methods of treating and/or preventing pathologic cardiac hypertrophy and heart failure comprising administering hydroxamate compounds which are deacetylase inhibitors.
  [FR] L'invention concerne des procédés permettant de traiter et/ou prévenir l'hypertrophie cardiaque et l'insuffisance cardiaque pathologiques, qui consistent à administrer des composés d'hydroxamate qui sont des inhibiteurs de la désacétylase.
• <i>N</i>-Hydroxy-3-phenyl-2-propenamides as Novel Inhibitors of Human Histone Deacetylase with in Vivo Antitumor Activity:  Discovery of (2<i>E</i>)-<i>N</i>-Hydroxy-3-[4-[[(2-hydroxyethyl)[2-(1<i>H</i>-indol-3-yl)ethyl]amino]methyl]phenyl]-2-propenamide (NVP-LAQ824)
  作者：Stacy W. Remiszewski、Lidia C. Sambucetti、Kenneth W. Bair、John Bontempo、David Cesarz、Nagarajan Chandramouli、Ru Chen、Min Cheung、Susan Cornell-Kennon、Karl Dean、George Diamantidis、Dennis France、Michael A. Green、Kobporn Lulu Howell、Rina Kashi、Paul Kwon、Peter Lassota、Mary S. Martin、Yin Mou、Lawrence B. Perez、Sushil Sharma、Troy Smith、Eric Sorensen、Francis Taplin、Nancy Trogani、Richard Versace、Heather Walker、Susan Weltchek-Engler、Alexander Wood、Arthur Wu、Peter Atadja

  DOI：10.1021/jm030235w

  日期：2003.10.1

  A series of N-hydroxy-3-phenyl-2-propenamides were prepared as novel inhibitors of human histone deacetylase (HDAC). These compounds were potent enzyme inhibitors, having IC(50)s < 400 nM in a partially purified enzyme assay. However, potency in cell growth inhibition assays ranged over 2 orders of magnitude in two human carcinoma cell lines. Selected compounds having cellular IC50 < 750 nM were tested for maximum tolerated dose (MTD) and for efficacy in the HCT116 human colon tumor xenograft assay. Four compounds having an MTD 100 mg/kg were selected for dose-response studies in the HCT116 xenograft model. One compound, 9 (NVP-LAQ824), had significant dose-related activity in the HCT116 colon and A549 lung tumor models, high MTD, and low gross toxicity. On the basis, in part, of these properties, 9 has entered human clinical trials in 2002.