1,2,3,4-tetrahydro-6,7-dimethoxy-2-[(4-nitrophenyl)sulfonyl]isoquinoline | 879473-33-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 1,2,3,4-tetrahydro-6,7-dimethoxy-2-[(4-nitrophenyl)sulfonyl]isoquinoline
• 英文别名: 6,7-dimethoxy-2-((4-nitrophenyl)sulfonyl)-1,2,3,4-tetrahydroisoquinoline；6,7-dimethoxy-2-(4-nitrophenyl)sulfonyl-3,4-dihydro-1H-isoquinoline
• CAS: 879473-33-3
• 化学式: C₁₇H₁₈N₂O₆S
• 分子量: 378.406
• InChiKey: KOUJERKYCQDCSV-UHFFFAOYSA-N

物化性质

• 沸点：
  568.0±60.0 °C(Predicted)
• 密度：
  1.378±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  110
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1,2,3,4-tetrahydro-6,7-dimethoxy-2-[(4-nitrophenyl)sulfonyl]isoquinoline 在 盐酸 、 tin(II) chloride dihdyrate 、 sodium nitrite 作用下， 以 乙醇 、 水 为溶剂， 反应 4.75h， 生成 2-((4-azidophenyl)sulfonyl)-6,7-dimethoxy-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  Design, synthesis and molecular docking studies of novel N-benzenesulfonyl-1,2,3,4-tetrahydroisoquinoline-based triazoles with potential anticancer activity

  摘要：

  A novel series of N-benzenesulfonyl-1,2,3,4-tetrahydroisoquinolines (14-33) containing triazole moiety were designed and synthesized through rational cycloadditions using the modified Pictet-Spengler reaction and the Click chemistry. Antiproliferative activity against four cancer cell lines (e.g., HuCCA-1, HepG2, A549 and MOLT-3) revealed that many substituted triazole analogs of benzoates (20, 29) and benzaldehydes (30,32) exhibited anticancer activity against all of the tested cancer cell lines in which the ester analog 20 was shown to be the most potent compound against HuCCA-1 (IC50=0.63 mu M) and A549 (IC50 = 0.57 mu M) cell lines. Triazoles bearing phenyl (15, 24), tolyl (26, 27), acetophenone (19), benzoate (20, 29), benzaldehyde (21, 30) and naphthalenyl (25) substituents showed stronger anticancer activity against HepG2 cells than that of the etoposide. Interestingly, the p-tolyl analog (27) displayed the most potent inhibitory activity (1050 = 0.56 mu M) against HepG2 cells without affecting normal cells. Of the investigated tetrahydroisoquinoline-triazoles, the promising compounds 20 and 27 were selected for molecular docking against AKR1C3, which was identified to be a plausible target site. (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.05.019
• 作为产物：
  描述：

  3,4-二甲氧基苯乙胺 在 sodium carbonate 作用下， 以 甲酸 、 二氯甲烷 为溶剂， 生成 1,2,3,4-tetrahydro-6,7-dimethoxy-2-[(4-nitrophenyl)sulfonyl]isoquinoline
  参考文献：
  名称：

  Synthesis and molecular docking of 1,2,3-triazole-based sulfonamides as aromatase inhibitors

  摘要：

  A series of 1,4-disubstituted-1,2,3-triazoles (13-35) containing sulfonamide moiety were synthesized and evaluated for their aromatase inhibitory effects. Most triazoles with open-chain sulfonamide showed significant aromatase inhibitory activity (IC50 = 1.3-9.4 mu M). Interestingly, the meta analog of triazole-benzene-sulfonamide (34) bearing 6,7-dimethoxy substituents on the isoquinoline ring displayed the most potent aromatase inhibitory activity (IC50 = 0.2 mu M) without affecting normal cell. Molecular docking of these triazoles against aromatase revealed that the compounds could snugly occupy the active site of the enzyme through hydrophobic, pi-pi stacking, and hydrogen bonding interactions. The potent compound 34 was able to form hydrogen bonds with Met374 and Ser478 which were suggested to be the essential residues for the promising inhibition. The study provides compound 34 as a potential lead molecule of anti-aromatase agent for further development. (C) 2015 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2015.04.036

文献信息

• Tungstophosphoric acid catalyzed synthesis of N-sulfonyl-1,2,3,4-tetrahydroisoquinoline analogs
  作者：Ratchanok Pingaew、Supaluk Prachayasittikul、Somsak Ruchirawat、Virapong Prachayasittikul

  DOI：10.1016/j.cclet.2013.06.019

  日期：2013.10

  An operationally simple and eco-friendly protocol has been developed for the synthesis of N-sulfonyl-1,2,3,4-tetrahydroisoquinolines 3 using the modified Pictet-Spengler reaction of N-sulfonylphenylethylamines 1 and various aldehydes 2 in the presence of tungstophosphoric acid hydrate. (C) 2013 Ratchanok Pingaew. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
• Novel 1,4-naphthoquinone-based sulfonamides: Synthesis, QSAR, anticancer and antimalarial studies
  作者：Ratchanok Pingaew、Veda Prachayasittikul、Apilak Worachartcheewan、Chanin Nantasenamat、Supaluk Prachayasittikul、Somsak Ruchirawat、Virapong Prachayasittikul

  DOI：10.1016/j.ejmech.2015.09.001

  日期：2015.10

  A novel series of 1,4-naphthoquinones (33-44) tethered by open and closed chain sulfonamide moieties were designed, synthesized and evaluated for their cytotoxic and antimalarial activities. All quinone-sulfonamide derivatives displayed a broad spectrum of cytotoxic activities against all of the tested cancer cell lines including HuCCA-1, HepG2, A549 and MOLT-3. Most quinones (33-36 and 38-43) exerted higher anticancer activity against HepG2 cell than that of the etoposide. The open chain analogs 36 and 42 were shown to be the most potent compounds. Notably, the restricted sulfonamide analog 38 with 6,7-dimethoxy groups exhibited the most potent antimalarial activity (IC50 = 2.8 mu M). Quantitative structure activity relationships (QSAR) study was performed to reveal important chemical features governing the biological activities. Five constructed QSAR models provided acceptable predictive performance (R-cv, 0.5647-0.9317 and RMSEcv 0.1231-0.2825). Four additional sets of structurally modified compounds were generated in silico (34a-34d, 36a-36k, 40a-40d and 42a-42k) in which their activities were predicted using the constructed QSAR models. A comprehensive discussion of the structure activity relationships was made and a set of promising compounds (i.e., 33, 36, 38, 42, 36d, 36f, 42e, 42g and 42f) was suggested for further development as anticancer and antimalarial agents. (C) 2015 Elsevier Masson SAS. All rights reserved.
• N-aryltetrahydroisoquinoline derivatives as HA-CD44 interaction inhibitors: Design, synthesis, computational studies, and antitumor effect
  作者：Jose M. Espejo-Román、Belén Rubio-Ruiz、Meriem Chayah-Ghaddab、Carlos Vega-Gutierrez、Gracia García-García、Arantza Muguruza-Montero、Carmen Domene、Rosario M. Sánchez-Martín、Olga Cruz-López、Ana Conejo-García

  DOI：10.1016/j.ejmech.2023.115570

  日期：2023.10
• Design, synthesis and molecular docking studies of novel N-benzenesulfonyl-1,2,3,4-tetrahydroisoquinoline-based triazoles with potential anticancer activity
  作者：Ratchanok Pingaew、Prasit Mandi、Chanin Nantasenamat、Supaluk Prachayasittikul、Somsak Ruchirawat、Virapong Prachayasittikul

  DOI：10.1016/j.ejmech.2014.05.019

  日期：2014.6

  A novel series of N-benzenesulfonyl-1,2,3,4-tetrahydroisoquinolines (14-33) containing triazole moiety were designed and synthesized through rational cycloadditions using the modified Pictet-Spengler reaction and the Click chemistry. Antiproliferative activity against four cancer cell lines (e.g., HuCCA-1, HepG2, A549 and MOLT-3) revealed that many substituted triazole analogs of benzoates (20, 29) and benzaldehydes (30,32) exhibited anticancer activity against all of the tested cancer cell lines in which the ester analog 20 was shown to be the most potent compound against HuCCA-1 (IC50=0.63 mu M) and A549 (IC50 = 0.57 mu M) cell lines. Triazoles bearing phenyl (15, 24), tolyl (26, 27), acetophenone (19), benzoate (20, 29), benzaldehyde (21, 30) and naphthalenyl (25) substituents showed stronger anticancer activity against HepG2 cells than that of the etoposide. Interestingly, the p-tolyl analog (27) displayed the most potent inhibitory activity (1050 = 0.56 mu M) against HepG2 cells without affecting normal cells. Of the investigated tetrahydroisoquinoline-triazoles, the promising compounds 20 and 27 were selected for molecular docking against AKR1C3, which was identified to be a plausible target site. (C) 2014 Elsevier Masson SAS. All rights reserved.
• Synthesis and molecular docking of 1,2,3-triazole-based sulfonamides as aromatase inhibitors
  作者：Ratchanok Pingaew、Veda Prachayasittikul、Prasit Mandi、Chanin Nantasenamat、Supaluk Prachayasittikul、Somsak Ruchirawat、Virapong Prachayasittikul

  DOI：10.1016/j.bmc.2015.04.036

  日期：2015.7

  A series of 1,4-disubstituted-1,2,3-triazoles (13-35) containing sulfonamide moiety were synthesized and evaluated for their aromatase inhibitory effects. Most triazoles with open-chain sulfonamide showed significant aromatase inhibitory activity (IC50 = 1.3-9.4 mu M). Interestingly, the meta analog of triazole-benzene-sulfonamide (34) bearing 6,7-dimethoxy substituents on the isoquinoline ring displayed the most potent aromatase inhibitory activity (IC50 = 0.2 mu M) without affecting normal cell. Molecular docking of these triazoles against aromatase revealed that the compounds could snugly occupy the active site of the enzyme through hydrophobic, pi-pi stacking, and hydrogen bonding interactions. The potent compound 34 was able to form hydrogen bonds with Met374 and Ser478 which were suggested to be the essential residues for the promising inhibition. The study provides compound 34 as a potential lead molecule of anti-aromatase agent for further development. (C) 2015 Elsevier Ltd. All rights reserved.