2-((3-aminophenyl)sulfonyl)-1,2,3,4-tetrahydroisoquinoline | 91619-42-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2-((3-aminophenyl)sulfonyl)-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 3-((3,4-dihydroisoquinolin-2(1H)-yl)sulfonyl)aniline；3-(3,4-dihydro-1H-isoquinolin-2-ylsulfonyl)aniline
• CAS: 91619-42-0
• 化学式: C₁₅H₁₆N₂O₂S
• 分子量: 288.37
• InChiKey: PFLQKTXITFDFRF-UHFFFAOYSA-N

物化性质

• 熔点：
  202-203 °C(Solv: methanol (67-56-1); water (7732-18-5))
• 沸点：
  513.5±60.0 °C(Predicted)
• 密度：
  1.329±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  71.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-((3-aminophenyl)sulfonyl)-1,2,3,4-tetrahydroisoquinoline 在 盐酸 、 sodium azide 、 copper(ll) sulfate pentahydrate 、 (+)-sodium ascorbate 、 sodium nitrite 作用下， 以 水 、 溶剂黄146 、 叔丁醇 为溶剂， 反应 12.5h， 生成 4-((1-(3-((3,4-dihydroisoquinolin-2(1H)-yl)sulfonyl)phenyl)-1H-1,2,3-triazol-4-yl)methoxy)-2H-chromen-2-one
  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
• 作为产物：
  描述：

  3-硝基苯磺酰氯 在 吡啶 、 铁粉 、 溶剂黄146 作用下， 以 乙醇 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 2-((3-aminophenyl)sulfonyl)-1,2,3,4-tetrahydroisoquinoline
  参考文献：
  名称：

  3-(3,4-Dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic Acids: Highly Potent and Selective Inhibitors of the Type 5 17-β-Hydroxysteroid Dehydrogenase AKR1C3

  摘要：

  A high-throughput screen identified 3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acid as a novel, highly potent (low nM), and isoform-selective (1500-fold) inhibitor of aldo-keto reductase AKR1C3: a target of interest in both breast and prostate cancer. Crystal structure studies showed that the carboxylate group occupies the oxyanion hole in the enzyme, while the sulfonamide provides the correct twist to allow the dihydroisoquinoline to bind in an adjacent hydrophobic pocket. SAR studies around this lead showed that the positioning of the carboxylate was critical, although it could be substituted by acid isosteres and amides. Small substituents on the dihydroisoquinoline gave improvements in potency. A set of "reverse sulfonamides" showed a 12-fold preference for the R stereoisomer. The compounds showed good cellular potency, as measured by inhibition of AKR1C3 metabolism of a known dinitrobenzamide substrate, with a broad rank order between enzymic and cellular activity, but amide analogues were more effective than predicted by the cellular assay.

  DOI：

  10.1021/jm3007867

文献信息

• 3-(3,4-Dihydroisoquinolin-2(1<i>H</i>)-ylsulfonyl)benzoic Acids: Highly Potent and Selective Inhibitors of the Type 5 17-β-Hydroxysteroid Dehydrogenase AKR1C3
  作者：Stephen M. F. Jamieson、Darby G. Brooke、Daniel Heinrich、Graham J. Atwell、Shevan Silva、Emma J. Hamilton、Andrew P. Turnbull、Laurent J. M. Rigoreau、Elisabeth Trivier、Christelle Soudy、Sharon S. Samlal、Paul J. Owen、Ewald Schroeder、Tony Raynham、Jack U. Flanagan、William A. Denny

  DOI：10.1021/jm3007867

  日期：2012.9.13

  A high-throughput screen identified 3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acid as a novel, highly potent (low nM), and isoform-selective (1500-fold) inhibitor of aldo-keto reductase AKR1C3: a target of interest in both breast and prostate cancer. Crystal structure studies showed that the carboxylate group occupies the oxyanion hole in the enzyme, while the sulfonamide provides the correct twist to allow the dihydroisoquinoline to bind in an adjacent hydrophobic pocket. SAR studies around this lead showed that the positioning of the carboxylate was critical, although it could be substituted by acid isosteres and amides. Small substituents on the dihydroisoquinoline gave improvements in potency. A set of "reverse sulfonamides" showed a 12-fold preference for the R stereoisomer. The compounds showed good cellular potency, as measured by inhibition of AKR1C3 metabolism of a known dinitrobenzamide substrate, with a broad rank order between enzymic and cellular activity, but amide analogues were more effective than predicted by the cellular assay.
• 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.
• KEMPTER, G.;BEERBALK, H. -D., WISS. Z. PAED. HOCHSCH. K. LEBKNECHT POTSDAM, 1983, 27, N 1, 101-120
  作者：KEMPTER, G.、BEERBALK, H. -D.

  DOI：——

  日期：——
• 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.