methyl 6-{[(E)-3-(8-quinolinyl)-2-propenoyl]amino}hexanoate | 1147683-03-1

• 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: methyl 6-{[(E)-3-(8-quinolinyl)-2-propenoyl]amino}hexanoate
• 英文别名: methyl 6-[[(E)-3-quinolin-8-ylprop-2-enoyl]amino]hexanoate
• CAS: 1147683-03-1
• 化学式: C₁₉H₂₂N₂O₃
• 分子量: 326.395
• InChiKey: AEIONNSNQHKKES-VAWYXSNFSA-N

物化性质

• 沸点：
  550.3±50.0 °C(predicted)
• 密度：
  1.154±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  68.3
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl 6-{[(E)-3-(8-quinolinyl)-2-propenoyl]amino}hexanoate 在 盐酸羟胺 、 sodium methylate 作用下， 以 甲醇 为溶剂， 以52%的产率得到(E)-N-[6-(hydroxyamino)-6-oxohexyl]-3-(8-quinolinyl)-2-propenamide
  参考文献：
  名称：

  Novel amide derivatives as inhibitors of histone deacetylase: Design, synthesis and SAR

  摘要：

  Enzymatic inhibition of histone deacetylase (HDAC) activity is emerging as an innovative and effective approach for the treatment of cancer. A series of novel amide derivatives have been synthesized and evaluated for their ability to inhibit human HDACs. Multiple compounds were identified as potent HDAC inhibitors (HDACi), with IC50 values in the low nanomolar (W) range against enzyme activity in HeLa cell extracts and sub-mu M for their in vitro anti-proliferative effect on cell lines. The introduction of an unsaturated linking group between the terminal aryl ring and the amide moiety was the key to obtain good potency. This approach yielded compounds such as (E)-N-[6-(hydroxyamino)-6-oxohexyl]-3-(7-quinolinyl)-2-propenamide (27) (HDAC IC50 8 nM) which showed potent in vivo activity in the P388 mouse leukemia syngeneic model (an increased lifespan (ILS) of 111% was obtained). (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.06.020
• 作为产物：
  描述：

  6-氨基己酸甲酯 盐酸盐 、 (2E)-3-(quinolin-8-yl)prop-2-enoic acid 在 N,N'-羰基二咪唑 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 以46%的产率得到methyl 6-{[(E)-3-(8-quinolinyl)-2-propenoyl]amino}hexanoate
  参考文献：
  名称：

  Novel amide derivatives as inhibitors of histone deacetylase: Design, synthesis and SAR

  摘要：

  Enzymatic inhibition of histone deacetylase (HDAC) activity is emerging as an innovative and effective approach for the treatment of cancer. A series of novel amide derivatives have been synthesized and evaluated for their ability to inhibit human HDACs. Multiple compounds were identified as potent HDAC inhibitors (HDACi), with IC50 values in the low nanomolar (W) range against enzyme activity in HeLa cell extracts and sub-mu M for their in vitro anti-proliferative effect on cell lines. The introduction of an unsaturated linking group between the terminal aryl ring and the amide moiety was the key to obtain good potency. This approach yielded compounds such as (E)-N-[6-(hydroxyamino)-6-oxohexyl]-3-(7-quinolinyl)-2-propenamide (27) (HDAC IC50 8 nM) which showed potent in vivo activity in the P388 mouse leukemia syngeneic model (an increased lifespan (ILS) of 111% was obtained). (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.06.020

文献信息

• Novel amide derivatives as inhibitors of histone deacetylase: Design, synthesis and SAR
  作者：Victor Andrianov、Vija Gailite、Daina Lola、Einars Loza、Valentina Semenikhina、Ivars Kalvinsh、Paul Finn、Kamille Dumong Petersen、James W.A. Ritchie、Nagma Khan

  DOI：10.1016/j.ejmech.2008.06.020

  日期：2009.3

  Enzymatic inhibition of histone deacetylase (HDAC) activity is emerging as an innovative and effective approach for the treatment of cancer. A series of novel amide derivatives have been synthesized and evaluated for their ability to inhibit human HDACs. Multiple compounds were identified as potent HDAC inhibitors (HDACi), with IC50 values in the low nanomolar (W) range against enzyme activity in HeLa cell extracts and sub-mu M for their in vitro anti-proliferative effect on cell lines. The introduction of an unsaturated linking group between the terminal aryl ring and the amide moiety was the key to obtain good potency. This approach yielded compounds such as (E)-N-[6-(hydroxyamino)-6-oxohexyl]-3-(7-quinolinyl)-2-propenamide (27) (HDAC IC50 8 nM) which showed potent in vivo activity in the P388 mouse leukemia syngeneic model (an increased lifespan (ILS) of 111% was obtained). (C) 2008 Elsevier Masson SAS. All rights reserved.