2-(4-((2-methylpiperidin-1-yl)sulfonyl)phenyl)isoindoline-1,3-dione | 1430810-44-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: 2-(4-((2-methylpiperidin-1-yl)sulfonyl)phenyl)isoindoline-1,3-dione
• 英文别名: 2-[4-(2-Methylpiperidin-1-yl)sulfonylphenyl]isoindole-1,3-dione；2-[4-(2-methylpiperidin-1-yl)sulfonylphenyl]isoindole-1,3-dione
• CAS: 1430810-44-8
• 化学式: C₂₀H₂₀N₂O₄S
• 分子量: 384.456
• InChiKey: VGFCMULUCZSZNU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  27
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  83.1
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  2-甲基哌啶 在 palladium 10% on activated carbon 、 氢气 、 三乙胺 作用下， 以 二氯甲烷 、 二甲基亚砜 、 乙酸乙酯 为溶剂， 20.0~120.0 ℃ 、506.66 kPa 条件下， 反应 8.0h， 生成 2-(4-((2-methylpiperidin-1-yl)sulfonyl)phenyl)isoindoline-1,3-dione
  参考文献：
  名称：

  Synthesis and structure–activity relationships for 1-(4-(piperidin-1-ylsulfonyl)phenyl)pyrrolidin-2-ones as novel non-carboxylate inhibitors of the aldo-keto reductase enzyme AKR1C3

  摘要：

  High expression of the aldo-keto reductase enzyme AKR1C3 in the human prostate and breast has implicated it in the development and progression of leukemias and of prostate and breast cancers. Inhibitors are thus of interest as potential drugs. Most inhibitors of AKR1C3 are carboxylic acids, whose transport into cells is likely dominated by carrier-mediated processes. We describe here a series of (piperidinosulfonamidophenyl)pyrrolidin-2-ones as potent (<100 nM) and isoform-selective non-carboxylate inhibitors of AKR1C3. Structure-activity relationships identified the sulfonamide was critical, and a crystal structure showed the 2-pyrrolidinone does not interact directly with residues in the oxyanion hole. Variations in the position, co-planarity or electronic nature of the pyrrolidinone ring severely diminished activity, as did altering the size or polarity of the piperidino ring. There was a broad correlation between the enzyme potencies of the compounds and their effectiveness at inhibiting AKR1C3 activity in cells. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.01.047

文献信息

• Synthesis and molecular docking studies of some 4-phthalimidobenzenesulfonamide derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors
  作者：Zeynep Soyer、Sirin Uysal、Sulunay Parlar、Ayse Hande Tarikogullari Dogan、Vildan Alptuzun

  DOI：10.1080/14756366.2016.1226298

  日期：2017.1.1

  A series of 4-phthalimidobenzenesulfonamide derivatives were designed, synthesized and evaluated for the inhibitory activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Structures of the title compounds were confirmed by spectral and elemental analyses. The cholinesterase (ChE) inhibitory activity studies were carried out using Ellman's colorimetric method. The biological

  设计、合成了一系列4-邻苯二甲酰亚氨基苯磺酰胺衍生物，并评估了其对乙酰胆碱酯酶（AChE）和丁酰胆碱酯酶（BuChE）的抑制活性。通过光谱和元素分析确认了标题化合物的结构。使用埃尔曼比色法进行胆碱酯酶（ChE）抑制活性研究。生物活性结果表明，所有标题化合物（化合物8除外）均对AChE表现出高选择性。在测试的化合物中，化合物 7 对 AChE 的抑制作用最强 (IC50= 1.35 ± 0.08 μM)，而化合物 3 对 BuChE 的抑制作用最强 (IC50= 13.41 ± 0.62 μM)。对AChE中最活跃的化合物7的分子对接研究表明，该化合物可以与AChE的催化活性位点（CAS）和外周阴离子位点（PAS）相互作用。