3-butoxy-4-(hydroxy(methyl)amino)-3-cyclobutene-1,2-dione | 871917-43-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 3-butoxy-4-(hydroxy(methyl)amino)-3-cyclobutene-1,2-dione
• 英文别名: 3-butoxy-4-(hydroxy-methyl-amino)-cyclobut-3-ene-1,2-dione；3-Butoxy-4-[hydroxy(methyl)amino]cyclobut-3-ene-1,2-dione
• CAS: 871917-43-0
• 化学式: C₉H₁₃NO₄
• 分子量: 199.207
• InChiKey: CRCCXEYCPSJPCI-UHFFFAOYSA-N

物化性质

• 沸点：
  321.4±52.0 °C(Predicted)
• 密度：
  1.27±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.56
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  3-butoxy-4-(hydroxy(methyl)amino)-3-cyclobutene-1,2-dione 在 劳森试剂 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 (2S,3S)-2-[[2-[hydroxy(methyl)amino]-4-oxo-3-sulfanylidenecyclobuten-1-yl]amino]-3-methyl-N-[(2S)-1-(methylamino)-1-oxo-3-phenylpropan-2-yl]pentanamide
  参考文献：
  名称：

  Squaric Acid-Based Peptidic Inhibitors of Matrix Metalloprotease-1

  摘要：

  A series of squaric acid-peptide conjugates were synthesized and evaluated as inhibitors of MMP-1. The cyclobut-3-enedione core was substituted at the 3-position with several functional groups, such as -N(alkyl)OH, -NHOH, and -OH, that are designed to bind to the zinc atom in the active site of the metalloprotease. The 4-position of the cyclobut-3-enedione was derivatized with mono- or dipeptides that are designed to bind in the S1' and S2' subsites of the enzyme, and position the metal chelating group appropriately in the active site for binding to zinc. Positional scanning revealed that -N(Me)OH provided the highest level of inhibition among the chelating groups that were tested, and Leu-Tle-NHMe was the preferred amino acid sequence. A combination of these groups yielded an inhibitor with an IC50 value of 95 mu M. For one inhibitor, conversion of one of the carbonyl groups on the cyclobut-3-enedione core to a thiocarbonyl group resulted in a 18-fold increase in potency, and yielded a compound with an IC50 value of 15 mu M.

  DOI：

  10.1021/jo0517848
• 作为产物：
  描述：

  方酸二正丁酯 、 N-甲基羟胺盐酸盐 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以65%的产率得到3-butoxy-4-(hydroxy(methyl)amino)-3-cyclobutene-1,2-dione
  参考文献：
  名称：

  Synthesis of a 200-member library of squaric acid N-hydroxylamide amides

  摘要：

  We report here the parallel synthesis of 200 compounds based on squaric acid template. These compounds are obtained via a one-step solution-phase procedure starting from three squaric acid N-hydroxylamide esters precursors. The set of diverse reagents qualified (amines, anilines, amino-alcohols and amino-esters) makes this strategy suitable for the search of biologically active compounds. The library was screened on the zinc metalloenzyme ADAMTS-5 and hits with IC50 in the range of 1-50 mu M were identified. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.08.025

文献信息

• Squaric Acid-Based Peptidic Inhibitors of Matrix Metalloprotease-1
  作者：M. Burak Onaran、Anthony B. Comeau、Christopher T. Seto

  DOI：10.1021/jo0517848

  日期：2005.12.1

  A series of squaric acid-peptide conjugates were synthesized and evaluated as inhibitors of MMP-1. The cyclobut-3-enedione core was substituted at the 3-position with several functional groups, such as -N(alkyl)OH, -NHOH, and -OH, that are designed to bind to the zinc atom in the active site of the metalloprotease. The 4-position of the cyclobut-3-enedione was derivatized with mono- or dipeptides that are designed to bind in the S1' and S2' subsites of the enzyme, and position the metal chelating group appropriately in the active site for binding to zinc. Positional scanning revealed that -N(Me)OH provided the highest level of inhibition among the chelating groups that were tested, and Leu-Tle-NHMe was the preferred amino acid sequence. A combination of these groups yielded an inhibitor with an IC50 value of 95 mu M. For one inhibitor, conversion of one of the carbonyl groups on the cyclobut-3-enedione core to a thiocarbonyl group resulted in a 18-fold increase in potency, and yielded a compound with an IC50 value of 15 mu M.
• Synthesis of a 200-member library of squaric acid N-hydroxylamide amides
  作者：Julie Charton、Benoît P. Déprez、Rébecca F. Déprez-Poulain

  DOI：10.1016/j.bmcl.2008.08.025

  日期：2008.9

  We report here the parallel synthesis of 200 compounds based on squaric acid template. These compounds are obtained via a one-step solution-phase procedure starting from three squaric acid N-hydroxylamide esters precursors. The set of diverse reagents qualified (amines, anilines, amino-alcohols and amino-esters) makes this strategy suitable for the search of biologically active compounds. The library was screened on the zinc metalloenzyme ADAMTS-5 and hits with IC50 in the range of 1-50 mu M were identified. (C) 2008 Elsevier Ltd. All rights reserved.