2-((3-bromophenyl)sulfonyl)-1,2,3,4-tetrahydroisoquinoline | 1022427-87-7

• 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: 2-((3-bromophenyl)sulfonyl)-1,2,3,4-tetrahydroisoquinoline
• 英文别名: 2-(3-bromophenyl)sulfonyl-3,4-dihydro-1H-isoquinoline
• CAS: 1022427-87-7
• 化学式: C₁₅H₁₄BrNO₂S
• 分子量: 352.252
• InChiKey: XIGPDIFQYVMNGM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 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：
  45.8
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-((3-bromophenyl)sulfonyl)-1,2,3,4-tetrahydroisoquinoline 、 在 tris-(dibenzylideneacetone)dipalladium(0) 、 lithium tert-butoxide 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 1,4-二氧六环 为溶剂， 生成
  参考文献：
  名称：

  10.1016/j.bioorg.2024.107458

  摘要：

  DOI：

  10.1016/j.bioorg.2024.107458
• 作为产物：
  描述：

  四氢异喹啉 、 3-溴苯磺酰氯 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 以8%的产率得到2-((3-bromophenyl)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

• Catalyst-free electrochemical sulfonylation of amines with sulfonyl hydrazide in aqueous medium
  作者：Wei Chen、Haojian Xu、Run Wu、Yang Chen、Pingbing Yu、Yanxi Jin

  DOI：10.1039/d3ob00690e

  日期：——

  with sulfonyl hydrazides under exogenous-oxidant-free and catalyst-free conditions in aqueous medium was developed. A wide variety of sulfonamides were prepared via a simple electrochemical process from various cyclic or acyclic secondary amines, as well as more challenging free primary amines with equivalent amount of aryl/heteroaryl hydrazides in air under mild conditions. This protocol was found

  开发了一种在水介质中、无外源氧化剂和无催化剂条件下，胺与磺酰肼的高效电化学磺酰化反应。在温和条件下，通过简单的电化学过程，由各种环状或无环仲胺以及更具挑战性的游离伯胺与等量的芳基/杂芳基酰肼在空气中制备了多种磺酰胺。该方案被发现在易于放大方面非常出色，并且在生物活性化合物的修饰/合成方面显示出巨大的潜力。通过一系列对照实验和CV研究对反应机理进行了研究，表明该反应可能经历了自由基途径。另外，n -Bu 4NBr 既作为支持电解质又作为氧化还原剂，从磺酰肼中产生磺酰自由基和磺酰阳离子。
• 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.
• 10.1016/j.bioorg.2024.107458
  作者：Bai, Xinyue、Yang, Yanling、Luo, Yilin、Zhang, Die、Zhai, Tianyu、Hu, Qianqian、Zhang, Ning、Dai, Qiangfang、Liang, Jiaxing、Bian, Hongyan、Liu, Xiaolong

  DOI：10.1016/j.bioorg.2024.107458

  日期：——