α-hydroxy-α-(7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophen-5-yl)acetic acid | 258520-68-2

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: α-hydroxy-α-(7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophen-5-yl)acetic acid
• 英文别名: 2-hydroxy-2-(7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophen-6-yl)acetic acid；2-hydroxy-2-(7-oxo-5,6-dihydro-4H-1-benzothiophen-6-yl)acetic acid
• CAS: 258520-68-2
• 化学式: C₁₀H₁₀O₄S
• 分子量: 226.253
• InChiKey: RPMJPSVBEWVNQH-UHFFFAOYSA-N

物化性质

• 沸点：
  483.4±30.0 °C(predicted)
• 密度：
  1.508±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  15
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  103
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  α-hydroxy-α-(7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophen-5-yl)acetic acid 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 1.5h， 以66%的产率得到4-hydroxy-4,4a,5,6-tetrahydrothieno[3,2-h]cinnolin-3(2H)-one
  参考文献：
  名称：

  5,6-二氢噻吩并[2,3- h ] cinnolin-3（2 H）-one和5,6-二氢噻吩并[3,2 - h ] cinnolin-3（2 H）-one对肼的行为。噻吩并噻吩啉酮和4-氨基噻吩并噻吩酮的合成

  摘要：

  异构体化合物5,6-二氢噻吩并[2,3- h ] cinnolin-3（2 H）-one（7a）和5,6-二氢噻吩并[[3,2 - h ] cinnolin-3（2 H）-one （7b）当保持在回流的水合肼中时，迅速地互变异构成相应的1，4-二氢噻吩并噻吩啉酮8a，b。随着较长的反应时间，最初形成的8a，b脱氢成噻吩并噻吩酮9a，b，最终胺化为4-氨基噻吩并噻吩酮10a，b。此行为回想起有关5,6-dihydrobenzocinnolin-3（2 H）-one（1）在相同条件下经历脱氢反应生成苯并[ h ]肉桂醇-3（2 H）-一（2），然后进行4胺化至3，但中间体的稳定性，最终胺化的机理有所不同，并获得更高的反应速率。所有这些差异可以根据两个系列的转化的中间体和产物的形成热来合理化。

  DOI：

  10.1002/jhet.5570360523
• 作为产物：
  描述：

  5,6-二氢-1-苯并噻吩-7(4H)-酮 、 乙醛酸 在 sodium hydroxide 作用下， 反应 1.0h， 以60%的产率得到α-hydroxy-α-(7-oxo-4,5,6,7-tetrahydrobenzo[b]thiophen-5-yl)acetic acid
  参考文献：
  名称：

  Preparation of Thieno[3,2-h]cinnolinones as Matrix Metalloproteinase Inhibitors

  摘要：

  A new series of thieno[3,2-h]cinnolinone analogues was synthesized which is structurally related to 2,3,4,4a,5,6-hexahydro thieno[3,2-h]cinnolin-3-one 1, a weak inhibitor of the matrix metalloproteinase MMP-8 (human neutrophil collagenase). Preliminary SAR studies have shown that while C-4a-methyl, C-7-acetylamino, C-7 and C-8-nitro substitution, and C-4-C-4a olefination provided no increase in activity relative to 1, Cs-acetylamino substitution as in 5 and 8 was favourable. Moreover, to predict how the thieno[3,3-h]cinnolinone inhibitors might bind to MMP-8, the unsubstituted compound 9 was docked into the MMP-8 crystal structure. These studies revealed that inhibitor 9 does not seem to be able to coordinate the catalytically-active zinc ion but preferably interact with the peptide-binding region of the active site.

  DOI：

  10.1002/(sici)1521-4184(200002)333:2/3<37::aid-ardp37>3.0.co;2-v

文献信息

• Preparation of Thieno[3,2-h]cinnolinones as Matrix Metalloproteinase Inhibitors
  作者：Gérard A. Pinna、Maria M. Curzu、Gabriele Murineddu、Giorgio Chelucci、Giorgio Cignarella、Ernesto Menta、Hans W. Krell、Giulio Rastelli、Anna M. Ferrari

  DOI：10.1002/(sici)1521-4184(200002)333:2/3<37::aid-ardp37>3.0.co;2-v

  日期：2000.2

  A new series of thieno[3,2-h]cinnolinone analogues was synthesized which is structurally related to 2,3,4,4a,5,6-hexahydro thieno[3,2-h]cinnolin-3-one 1, a weak inhibitor of the matrix metalloproteinase MMP-8 (human neutrophil collagenase). Preliminary SAR studies have shown that while C-4a-methyl, C-7-acetylamino, C-7 and C-8-nitro substitution, and C-4-C-4a olefination provided no increase in activity relative to 1, Cs-acetylamino substitution as in 5 and 8 was favourable. Moreover, to predict how the thieno[3,3-h]cinnolinone inhibitors might bind to MMP-8, the unsubstituted compound 9 was docked into the MMP-8 crystal structure. These studies revealed that inhibitor 9 does not seem to be able to coordinate the catalytically-active zinc ion but preferably interact with the peptide-binding region of the active site.
• Behaviour of 5,6-dihydrothieno[2,3-<i>h</i>]cinnolin-3(2<i>H</i>)-one and 5,6-dihydrothieno[3,2-<i>h</i>]cinnolin-3(2<i>H</i>)-one towards hydrazine. Synthesis of thienocinnolinones and of 4-aminothienocinnolinones
  作者：Stefania Villa、Giorgio Cignarella、Michela M. Curzu、Gérard A. Pinna、Elena Pini、Lucio Toma

  DOI：10.1002/jhet.5570360523

  日期：1999.9

  isomeric compounds 5,6-dihydrothieno[2,3-h]cinnolin-3(2H)-one (7a) and 5,6-dihydrothieno-[3,2-h]cinnolin-3(2H)-one (7b) rapidly tautomerise to the corresponding 1,4-dihydrothienocinnolinones 8a,b when kept in refluxing hydrazine hydrate. With longer reaction times the initially formed 8a,b dehydrogenate to the thienocinnolinones 9a,b which eventually are aminated to 4-aminothienocinnolinones 10a,b. This behaviour

  异构体化合物5,6-二氢噻吩并[2,3- h ] cinnolin-3（2 H）-one（7a）和5,6-二氢噻吩并[[3,2 - h ] cinnolin-3（2 H）-one （7b）当保持在回流的水合肼中时，迅速地互变异构成相应的1，4-二氢噻吩并噻吩啉酮8a，b。随着较长的反应时间，最初形成的8a，b脱氢成噻吩并噻吩酮9a，b，最终胺化为4-氨基噻吩并噻吩酮10a，b。此行为回想起有关5,6-dihydrobenzocinnolin-3（2 H）-one（1）在相同条件下经历脱氢反应生成苯并[ h ]肉桂醇-3（2 H）-一（2），然后进行4胺化至3，但中间体的稳定性，最终胺化的机理有所不同，并获得更高的反应速率。所有这些差异可以根据两个系列的转化的中间体和产物的形成热来合理化。