(6,7-dihydroxy-[1]isoquinolyl)-(3,4-dihydroxy-phenyl)-ketone

• 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: (6,7-dihydroxy-[1]isoquinolyl)-(3,4-dihydroxy-phenyl)-ketone
• 英文别名: (6,7-Dihydroxy-[1]isochinolyl)-(3,4-dihydroxy-phenyl)-keton；(6,7-Dihydroxy-isoquinolin-1-yl)-(3,4-dihydroxy-phenyl)-methanone；(6,7-dihydroxyisoquinolin-1-yl)-(3,4-dihydroxyphenyl)methanone
• 化学式: C₁₆H₁₁NO₅
• 分子量: 297.267
• InChiKey: MXJOCCQOPDSMHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  111
• 氢给体数：
  4
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  重氮甲烷 、 乙醚 、 (6,7-dihydroxy-[1]isoquinolyl)-(3,4-dihydroxy-phenyl)-ketone 生成 罌粟啶
  参考文献：
  名称：

  Oberlin, Archiv der Pharmazie, 1927, p. 284

  摘要：

  DOI：
• 作为产物：
  描述：

  罂粟碱 在 三氯化铝 、 sodium dichromate 、 溶剂黄146 作用下， 生成 (6,7-dihydroxy-[1]isoquinolyl)-(3,4-dihydroxy-phenyl)-ketone
  参考文献：
  名称：

  Oberlin, Archiv der Pharmazie, 1927, p. 284

  摘要：

  DOI：

文献信息

• DE444587
  申请人：——

  公开号：——

  公开（公告）日：——
• Oberlin, Archiv der Pharmazie, 1927, p. 284
  作者：Oberlin

  DOI：——

  日期：——
• 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.