3-(3,4-dihydroisoquinolin-2(1H)-yl)-N-phenylpropanamide | 498535-29-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 3-(3,4-dihydroisoquinolin-2(1H)-yl)-N-phenylpropanamide
• 英文别名: 3-(3,4-dihydro-2(1H)-isoquinolinyl)-N-phenylpropanamide；3-(3,4-dihydro-1H-isoquinolin-2-yl)-N-phenylpropanamide
• CAS: 498535-29-8
• 化学式: C₁₈H₂₀N₂O
• 分子量: 280.37
• InChiKey: HYQLDXYGOJREDF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  32.3
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为产物：
  描述：

  苯胺 在 三乙胺 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 反应 0.17h， 生成 3-(3,4-dihydroisoquinolin-2(1H)-yl)-N-phenylpropanamide
  参考文献：
  名称：

  Discovery of new potent protein arginine methyltransferase 5 (PRMT5) inhibitors by assembly of key pharmacophores from known inhibitors

  摘要：

  Protein arginine methyltransferase 5 (PRMT5) is an epigenetics related enzyme that has been validated as a promising therapeutic target for human cancer. Up to now, two small molecule PRMT5 inhibitors has been put into phase I clinical trial. In the present study, a series of candidate molecules were designed by combining key pharmacophores of formerly reported PRMT5 inhibitors. The in vitro PRMT5 inhibitory testing of compound 4b14 revealed an IC50 of 2.71 mu M, exhibiting high selectivity over PRMT1 and PRMT4 (> 70-fold selective). As expected, 4b14 exhibited potent anti-proliferative activity against a panel of leukemia and lymphoma cells, including MV4-11, Pfeiffer, SU-DHL-4 and KARPAS-422. Besides, 4b14 showed significant cell cycle arrest and apoptosis-inducing effects, as well as reduced the cellular symmetric arginine dimethylation level of SmD3 protein. Finally, affinity profiling analysis indicated that hydrophobic interactions, pi-pi stacking and cation-pi actions made the major contributions to the overall binding affinity. This scaffold provides a new chemical template for further development of better lead compounds targeting PRMT5.

  DOI：

  10.1016/j.bmcl.2018.10.026

文献信息

• Synthesis, evaluation and molecular modelling studies of some novel 3-(3,4-dihydroisoquinolin-2(1H)-yl)-N-(substitutedphenyl) propanamides as HIV-1 non-nucleoside reverse transcriptase inhibitors
  作者：S. Murugesan、Swastika Ganguly、Giovanni Maga

  DOI：10.1007/s12039-010-0018-7

  日期：2010.3

  elemental analysis and spectral data. All the compounds were evaluated for their HIV-1 RT inhibitory activity. Among the synthesized compounds, 3-(3,4-dihydroisoquinolin-2(1H)-yl)-N-o-tolyl propanamide 3d and 3-(3,4-dihydroisoquinolin-2(1H)-yl)-N-(2,4,6-tribromophenyl)propanamide 3f were identified as significant inhibitors of HIV-1 reverse transcriptase with 56% and 43% residual RT activity respectively at

  通过使相应的3-氯-N-（芳基）丙酰胺反应合成了一系列新颖的十五种3-（3,4-二氢异喹啉-2（1H）-基）-N-（取代苯基）丙酰胺3（ao）。2（ao）与1,2,3,4-四氢异喹啉1的乙腈溶液。根据元素分析和光谱数据对化合物进行了表征。评价所有化合物的HIV-1 RT抑制活性。在合成的化合物中，3-（3,4-二氢异喹啉-2（1 H）-基）-无甲苯基丙酰胺3d和3-（3,4-二氢异喹啉-2（1 H））-基）-N-（2,4,6-三溴苯基）丙酰胺3f被确定为HIV-1逆转录酶的重要抑制剂，与40μM的最终浓度相比，其残留RT活性分别为56％和43％。标准药物依法韦仑。为了研究这些化合物的结合模式，还进行了HIV-1 RT（PDB ID 1rt2）对接研究。
• Ganguly, Swastika; Murugesan, Journal of the Indian Chemical Society, 2010, vol. 87, # 7, p. 879 - 885
  作者：Ganguly, Swastika、Murugesan

  DOI：——

  日期：——