8,9-dihydro-4-methoxy-7H-benzo[de]quinoline-2-carboxaldehyde | 934697-70-8

• 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: 8,9-dihydro-4-methoxy-7H-benzo[de]quinoline-2-carboxaldehyde
• CAS: 934697-70-8
• 化学式: C₁₄H₁₃NO₂
• 分子量: 227.263
• InChiKey: KAIGBKDNEVIXQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.54
• 重原子数：
  17.0
• 可旋转键数：
  2.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  39.19
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  8,9-dihydro-4-methoxy-7H-benzo[de]quinoline-2-carboxaldehyde 、 氰甲基磷酸二乙酯 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以73%的产率得到β-[8,9-dihydro-4-methoxy-7H-benzo[de]quinolin-2-yl]propenonitrile
  参考文献：
  名称：

  Design, synthesis and melatoninergic potency of new N-acyl 8,9-dihydro-4-methoxy-7H-2-benzo[de]quinolinalkanamines

  摘要：

  A series of new N-acyl 8,9-dihydro-4-metlioxy-7H-2-benzo[de]quinolinalkanamines have been prepared and tested for their ability to activate pigment granule aggregation in Xenopus laevis melanophores and bind to the recombinant human MT1 and MT2 melatonin receptor subtypes expressed in NIH 3T3 cells. Compounds with a single methylene spacer in the side chain (7) have no agonist activity, but are weak antagonists in the Xenopus melanophore assay, irrespectively of the size or shape of the R substituent (R = CH3 to c-C4H7). In contrast, compounds with two (8) or three (9) methylene spacers show partial agonist activity, though this does vary with the nature of the R substituent. Interestingly, the cyclopropane and cyclobutane R substituents, which are usually linked with antagonism, render the cyclopropanecarboxamido analog 9d and its cyclobutane-carboxamido congener 9e weak agonists. It seems, therefore, that in these compounds the R substituent constitutes a functional probe in the dynamic agonist-antagonist conformational equilibrium. One of the new molecules, antagonist 8c, exhibits a noteworthy MT2 subtype selectivity (13-fold), whereas the acetamido analog 9a (with a three methylene units spacer) also acts as an antagonist and is the only analog exhibiting MT1 selectivity (> 10-fold). In contrast to the analogous N1-C7 annulated indole derivatives, recently reported, the new C1-C8 condensed isoquinolines are not all pure antagonists. Despite their modest receptor affinity at the binding site these compounds demonstrate that the nature of the response (agonist or antagonist activity) is dependent, in this case, on both the side chain spacer's length and the size and shape of the R group. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2006.11.006
• 作为产物：
  描述：

  methyl 8,9-dihydro-4-methoxy-7H-benzoquinoline-2-carboxylate 在 二异丁基氢化铝 作用下， 以 甲苯 为溶剂， 反应 0.42h， 以70%的产率得到8,9-dihydro-4-methoxy-7H-benzo[de]quinoline-2-carboxaldehyde
  参考文献：
  名称：

  Design, synthesis and melatoninergic potency of new N-acyl 8,9-dihydro-4-methoxy-7H-2-benzo[de]quinolinalkanamines

  摘要：

  A series of new N-acyl 8,9-dihydro-4-metlioxy-7H-2-benzo[de]quinolinalkanamines have been prepared and tested for their ability to activate pigment granule aggregation in Xenopus laevis melanophores and bind to the recombinant human MT1 and MT2 melatonin receptor subtypes expressed in NIH 3T3 cells. Compounds with a single methylene spacer in the side chain (7) have no agonist activity, but are weak antagonists in the Xenopus melanophore assay, irrespectively of the size or shape of the R substituent (R = CH3 to c-C4H7). In contrast, compounds with two (8) or three (9) methylene spacers show partial agonist activity, though this does vary with the nature of the R substituent. Interestingly, the cyclopropane and cyclobutane R substituents, which are usually linked with antagonism, render the cyclopropanecarboxamido analog 9d and its cyclobutane-carboxamido congener 9e weak agonists. It seems, therefore, that in these compounds the R substituent constitutes a functional probe in the dynamic agonist-antagonist conformational equilibrium. One of the new molecules, antagonist 8c, exhibits a noteworthy MT2 subtype selectivity (13-fold), whereas the acetamido analog 9a (with a three methylene units spacer) also acts as an antagonist and is the only analog exhibiting MT1 selectivity (> 10-fold). In contrast to the analogous N1-C7 annulated indole derivatives, recently reported, the new C1-C8 condensed isoquinolines are not all pure antagonists. Despite their modest receptor affinity at the binding site these compounds demonstrate that the nature of the response (agonist or antagonist activity) is dependent, in this case, on both the side chain spacer's length and the size and shape of the R group. (c) 2006 Elsevier Inc. All rights reserved.

  DOI：

  10.1016/j.bioorg.2006.11.006