3-(4-[[(tert-butoxycarbonyl)(3-phenylpropyl)amino]methyl]phenyl)-(2E)-2-propenoic acid | 619324-68-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: 3-(4-[[(tert-butoxycarbonyl)(3-phenylpropyl)amino]methyl]phenyl)-(2E)-2-propenoic acid
• 英文别名: (E)-3-[4-[[(2-methylpropan-2-yl)oxycarbonyl-(3-phenylpropyl)amino]methyl]phenyl]prop-2-enoic acid
• CAS: 619324-68-4
• 化学式: C₂₄H₂₉NO₄
• 分子量: 395.499
• InChiKey: KSWRUEZWCARSKB-FOCLMDBBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(4-[[(tert-butoxycarbonyl)(3-phenylpropyl)amino]methyl]phenyl)-(2E)-2-propenoic acid 在 N-甲基吗啉 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 N-hydroxy-3-[4-[[[3-phenylpropyl]amino]methyl]phenyl]-(2E)-2-propenamide trifluoroacetate
  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
• 作为产物：
  描述：

  3-(4-甲酰基苯基)丙-2-烯酸 在 sodium cyanoborohydride 、 溶剂黄146 、 三乙胺 作用下， 以 1,4-二氧六环 、 甲醇 、 水 为溶剂， 反应 2.0h， 生成 3-(4-[[(tert-butoxycarbonyl)(3-phenylpropyl)amino]methyl]phenyl)-(2E)-2-propenoic acid
  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。
• <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.