N¹-(2-(1H-indol-2-yl)quinazolin-4-yl)-N³,N³-dimethylpropane-1,3-diamine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N¹-(2-(1H-indol-2-yl)quinazolin-4-yl)-N³,N³-dimethylpropane-1,3-diamine
• 英文别名: N1-(2-(1H-indol-2-yl)quinazolin-4-yl)-N3,N3-dimethylpropane-1,3-diamine (9a)；N-[2-(1H-indol-2-yl)quinazolin-4-yl]-N',N'-dimethylpropane-1,3-diamine
• 化学式: C₂₁H₂₃N₅
• 分子量: 345.447
• InChiKey: TUDBLFNBEBPPHA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  56.8
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  2-(1-bromoethyl)quinazolin-4(3H)-one 在 三乙胺 、 三氯氧磷 作用下， 以 乙醇 为溶剂， 反应 30.0h， 生成 N¹-(2-(1H-indol-2-yl)quinazolin-4-yl)-N³,N³-dimethylpropane-1,3-diamine
  参考文献：
  名称：

  设计，合成和生物学评估作为3T3-L1脂肪细胞中脂肪生成/脂肪生成的潜在抑制剂的新型布加达汀类似物

  摘要：

  抑制脂肪细胞的分化和减少脂质的合成是治疗肥胖相关的代谢性疾病的有效方法。Bouchardatine（Bou）是一种天然生物碱，据报道可适度抑制3T3-L1细胞的分化而不会引起毒性。为了探索在Bou的8位a位置醛基的重要性并优化活性，我们通过丢弃或用卤素取代醛基并在Bou的5位置处引入不同的胺链，合成了35种（31种新型）化合物。使用基于细胞的筛选系统评估了降脂活性。小组在8 a的替换化合物的位置对降低脂质的活性很重要，并讨论了SAR。选择性化合物6e中显示出它的降脂作用的93倍增加（EC 50 相比= 0.24μM）和尚（EC 50  ≈25μM）。进一步的机理研究表明，化合物6e激活了AMP激活的蛋白激酶（AMPK）通路，并抑制MCE活性以阻止细胞增殖并诱导分化早期的细胞周期停滞，从而降低了脂肪形成因子的表达和脂肪酸合成相关蛋白质。

  DOI：

  10.1016/j.ejmech.2018.01.089

文献信息

• 2-(2-indolyl-)-4(3<i>H</i>)-quinazolines derivates as new inhibitors of AChE: design, synthesis, biological evaluation and molecular modelling
  作者：Zeng Li、Bin Wang、Jin-Qiang Hou、Shi-Liang Huang、Tian-Miao Ou、Jia-Heng Tan、Lin-Kun An、Ding Li、Lian-Quan Gu、Zhi-Shu Huang

  DOI：10.3109/14756366.2012.663363

  日期：2013.6.1

  We recently reported that synthetic derivatives of rutaecarpine alkaloid exhibited high acetyl cholinesterase (AChE) inhibitory activity and high selectivity for AChE over butyrylcholinesterases (BuChE). To explore novel effective drugs for the treatment of Alzheimer's disease (AD), in this paper, further research results were presented. Starting from a structure-based drug design, a series of novel 2-(2-indolyl-)-4(3H)-quinazolines derivates were designed and synthesized as the ring-opened analogues of rutaecarpine alkaloid and subjected to pharmacological evaluation as AChE inhibitors. Among them, derivates 3a-c and 3g-h exhibited strong inhibitory activity for AChE and high selectivity for AChE over BuChE. The structure-activity relationships were discussed and their binding conformation and simultaneous interactions mode were further clarified by kinetic characterization and the molecular docking studies.
• [EN] ANTI-PARASITIC SUBSTITUTED RING FUSED AZINE COMPOUNDS<br/>[FR] COMPOSÉS AZINES À NOYAUX CONDENSÉS SUBSTITUÉS, ANTIPARASITAIRES
  申请人：PARACO TECHNOLOGY LTD

  公开号：WO2012046207A1

  公开（公告）日：2012-04-12

  The present invention relates to substituted ring fused azine compounds for treating parasitic infections, in particular helminth infections. The present invention also relates to veterinary compositions comprising the compounds, uses of the compounds in the manufacture of medicaments, and methods of treating parasitic infections.
• Design, synthesis and biological evaluation of novel bouchardatine analogs as potential inhibitors of adipogenesis/lipogenesis in 3T3-L1 adipocytes
  作者：Lin Gao、Zhao Xu、Yong Rao、Yu-Ting Lu、Yu-Tao Hu、Hong Yu、Yao-Hao Xu、Qing-Qing Song、Ji-Ming Ye、Zhi-Shu Huang

  DOI：10.1016/j.ejmech.2018.01.089

  日期：2018.3

  Inhibition of the differentiation of adipocytes and reduced lipid synthesis are efficacious approaches for treating obesity-related metabolic disorders. Bouchardatine (Bou) is a natural alkaloid that has been reported to moderately inhibit the differentiation of 3T3-L1 cells without inducing toxicity. To explore the importance of aldehyde group at 8a-position of Bou and optimize the activity, we synthesized

  抑制脂肪细胞的分化和减少脂质的合成是治疗肥胖相关的代谢性疾病的有效方法。Bouchardatine（Bou）是一种天然生物碱，据报道可适度抑制3T3-L1细胞的分化而不会引起毒性。为了探索在Bou的8位a位置醛基的重要性并优化活性，我们通过丢弃或用卤素取代醛基并在Bou的5位置处引入不同的胺链，合成了35种（31种新型）化合物。使用基于细胞的筛选系统评估了降脂活性。小组在8 a的替换化合物的位置对降低脂质的活性很重要，并讨论了SAR。选择性化合物6e中显示出它的降脂作用的93倍增加（EC 50 相比= 0.24μM）和尚（EC 50  ≈25μM）。进一步的机理研究表明，化合物6e激活了AMP激活的蛋白激酶（AMPK）通路，并抑制MCE活性以阻止细胞增殖并诱导分化早期的细胞周期停滞，从而降低了脂肪形成因子的表达和脂肪酸合成相关蛋白质。