1-(3,4-dimethoxybenzyl)-3-ethoxycarbonyl-6,7-dimethoxyisoquinoline | 377733-24-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 1-(3,4-dimethoxybenzyl)-3-ethoxycarbonyl-6,7-dimethoxyisoquinoline
• 英文别名: 6,7-dimethoxy-1-veratryl-isoquinoline-3-carboxylic acid ethyl ester；6,7-Dimethoxy-1-veratryl-isochinolin-3-carbonsaeure-aethylester；Ethyl 1-(3,4-dimethoxybenzyl)-6,7-dimethoxyisoquinoline-3-carboxylate；ethyl 1-[(3,4-dimethoxyphenyl)methyl]-6,7-dimethoxyisoquinoline-3-carboxylate
• CAS: 377733-24-9
• 化学式: C₂₃H₂₅NO₆
• 分子量: 411.455
• InChiKey: SRSPOGFFSQMYNW-UHFFFAOYSA-N

物化性质

• 熔点：
  141 °C
• 沸点：
  565.1±50.0 °C(Predicted)
• 密度：
  1.187±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  9
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  76.1
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-(3,4-dimethoxybenzyl)-3-ethoxycarbonyl-6,7-dimethoxyisoquinoline 在 selenium(IV) oxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.5h， 以19.5 g的产率得到1-(3,4-Dimethoxy-benzoyl)-6,7-dimethoxy-isoquinoline-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Discovery of a Series of Nonpeptide Small Molecules That Inhibit the Binding of Insulin-like Growth Factor (IGF) to IGF-Binding Proteins

  摘要：

  Insulin-like growth factors (IGF-I and II) play an important role in metabolic and mitogenic activities through stimulation of the IGF-I receptor on the cell surface. Although the concentration of IGF in blood and cerebrospinal fluid is quite high (> 100 nM), this large pool of IGF is biologically inactive because of its association with six distinct binding proteins, which form high-affinity complexes with IGF. Thus, inhibitors of IGF-binding proteins (IGFBPs), especially IGFBP-3, could potentially alter the distribution between the "free" and "bound" forms of IGF and thereby elevate biologically active IGF-I to exert a beneficial effect on those patients with diseases that respond to the application of exogenous IGF-I. Whereas IGF-I peptide variants, which bind to IGFBPs but not the IGF-I receptor, have been shown to be potent IGF/IGFBP inhibitors, small molecule nonpeptide IGF/IGFBP inhibitors have the potential advantages of oral bioavailability and flexible dosing regimen. Here we report the discovery of several isoquinoline analogues, exemplified by I and 2, which bind IGFBP-3 as well as other IGFBPs at low nanomolar concentrations. More importantly, both compounds were shown to be able to release biologically active IGF-I from the IGF-I/IGFBP-3 complex. These results point to the feasibility of developing orally active therapeutics to treat IGF-responsive diseases by optimization of the lead molecules 1 and 2.

  DOI：

  10.1021/jm010304b
• 作为产物：
  描述：

  3,4-二甲氧基苯乙酸 在 草酰氯 、 sodium carbonate 、 sulfur 、 三氯氧磷 作用下， 以 乙酸乙酯 、 乙腈 为溶剂， 反应 18.5h， 生成 1-(3,4-dimethoxybenzyl)-3-ethoxycarbonyl-6,7-dimethoxyisoquinoline
  参考文献：
  名称：

  Discovery of a Series of Nonpeptide Small Molecules That Inhibit the Binding of Insulin-like Growth Factor (IGF) to IGF-Binding Proteins

  摘要：

  Insulin-like growth factors (IGF-I and II) play an important role in metabolic and mitogenic activities through stimulation of the IGF-I receptor on the cell surface. Although the concentration of IGF in blood and cerebrospinal fluid is quite high (> 100 nM), this large pool of IGF is biologically inactive because of its association with six distinct binding proteins, which form high-affinity complexes with IGF. Thus, inhibitors of IGF-binding proteins (IGFBPs), especially IGFBP-3, could potentially alter the distribution between the "free" and "bound" forms of IGF and thereby elevate biologically active IGF-I to exert a beneficial effect on those patients with diseases that respond to the application of exogenous IGF-I. Whereas IGF-I peptide variants, which bind to IGFBPs but not the IGF-I receptor, have been shown to be potent IGF/IGFBP inhibitors, small molecule nonpeptide IGF/IGFBP inhibitors have the potential advantages of oral bioavailability and flexible dosing regimen. Here we report the discovery of several isoquinoline analogues, exemplified by I and 2, which bind IGFBP-3 as well as other IGFBPs at low nanomolar concentrations. More importantly, both compounds were shown to be able to release biologically active IGF-I from the IGF-I/IGFBP-3 complex. These results point to the feasibility of developing orally active therapeutics to treat IGF-responsive diseases by optimization of the lead molecules 1 and 2.

  DOI：

  10.1021/jm010304b

文献信息

• DE674400
  申请人：——

  公开号：——

  公开（公告）日：——
• Discovery of a Series of Nonpeptide Small Molecules That Inhibit the Binding of Insulin-like Growth Factor (IGF) to IGF-Binding Proteins
  作者：Chen、Yun-Fei Zhu、Xin-Jun Liu、Zi-Xian Lu、Qiu Xie、Nicholas Ling

  DOI：10.1021/jm010304b

  日期：2001.11.1

  Insulin-like growth factors (IGF-I and II) play an important role in metabolic and mitogenic activities through stimulation of the IGF-I receptor on the cell surface. Although the concentration of IGF in blood and cerebrospinal fluid is quite high (> 100 nM), this large pool of IGF is biologically inactive because of its association with six distinct binding proteins, which form high-affinity complexes with IGF. Thus, inhibitors of IGF-binding proteins (IGFBPs), especially IGFBP-3, could potentially alter the distribution between the "free" and "bound" forms of IGF and thereby elevate biologically active IGF-I to exert a beneficial effect on those patients with diseases that respond to the application of exogenous IGF-I. Whereas IGF-I peptide variants, which bind to IGFBPs but not the IGF-I receptor, have been shown to be potent IGF/IGFBP inhibitors, small molecule nonpeptide IGF/IGFBP inhibitors have the potential advantages of oral bioavailability and flexible dosing regimen. Here we report the discovery of several isoquinoline analogues, exemplified by I and 2, which bind IGFBP-3 as well as other IGFBPs at low nanomolar concentrations. More importantly, both compounds were shown to be able to release biologically active IGF-I from the IGF-I/IGFBP-3 complex. These results point to the feasibility of developing orally active therapeutics to treat IGF-responsive diseases by optimization of the lead molecules 1 and 2.