2,6-difluoro-4-(1H-pyrrol-1-yl)phenol | 694496-27-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯
• 英文名称: 2,6-difluoro-4-(1H-pyrrol-1-yl)phenol
• 英文别名: 2,6-difluoro-4-pyrrol-1-yl-phenol；2,6-difluoro-4-pyrrol-1-ylphenol
• CAS: 694496-27-0
• 化学式: C₁₀H₇F₂NO
• 分子量: 195.168
• InChiKey: SLMOALIKKMWJLM-UHFFFAOYSA-N

物化性质

• 熔点：
  53-55 °C(Solv: ligroine (8032-32-4))
• 沸点：
  269.2±40.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  25.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2,6-difluoro-4-(1H-pyrrol-1-yl)phenol 在 sodium hydroxide 、 三氯化铝 、 四丁基硫酸氢铵 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 26.0h， 生成 [1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone
  参考文献：
  名称：

  [1-(3,5-Difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone as a Bioisostere of a Carboxylic Acid Aldose Reductase Inhibitor

  摘要：

  [1-(3,5-Difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone (6) was synthesized as a putative bioisostere of the known aldose reductase (AR) inhibitor (3-benzoylpyrrol-1-yl)acetic acid (I). It was found that 6 is approximately 5 times more potent as an in vitro inhibitor of AR than I, with an IC50 value in the submicromolar range. Furthermore, 6 showed considerable activity in an in vitro experimental glycation model of diabetes mellitus. Our results support the notion that 6 might become a useful lead structure.

  DOI：

  10.1021/jm031060t
• 作为产物：
  描述：

  2,5-二甲氧基四氢呋喃 、 4-氨基-2,6-二氟苯酚盐酸盐 在 4-氯吡啶 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以86%的产率得到2,6-difluoro-4-(1H-pyrrol-1-yl)phenol
  参考文献：
  名称：

  [1-(3,5-Difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone as a Bioisostere of a Carboxylic Acid Aldose Reductase Inhibitor

  摘要：

  [1-(3,5-Difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone (6) was synthesized as a putative bioisostere of the known aldose reductase (AR) inhibitor (3-benzoylpyrrol-1-yl)acetic acid (I). It was found that 6 is approximately 5 times more potent as an in vitro inhibitor of AR than I, with an IC50 value in the submicromolar range. Furthermore, 6 showed considerable activity in an in vitro experimental glycation model of diabetes mellitus. Our results support the notion that 6 might become a useful lead structure.

  DOI：

  10.1021/jm031060t

文献信息

• Structure–activity relations on [1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone. The effect of methoxy substitution on aldose reductase inhibitory activity and selectivity
  作者：Maria Chatzopoulou、Eduard Mamadou、Maria Juskova、Cathrine Koukoulitsa、Ioannis Nicolaou、Milan Stefek、Vassilis J. Demopoulos

  DOI：10.1016/j.bmc.2011.01.009

  日期：2011.2

  Based on our previous work, we studied the effect of methoxy-substitution as well as the regioposition of the benzoyl-moiety of 4a [(1-(3,5-difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl)(phenyl)methanone]. On this basis, compounds 4b–c and 5a–c were synthesized and assayed for aldose and aldehyde reductase inhibitory activity. Furthermore, a 4,6-difluoro-5-hydroxyphenyl pattern (9) was studied, in order

  基于我们以前的工作，我们研究了甲氧基取代的影响以及4a [（1-（3,5-difluoro-4-hydroxyphenyl）-1 H -pyrrol-3-yl ）（苯基）甲酮]。在此基础上，合成了化合物4b–c和5a–c，并测定了醛糖和醛还原酶的抑制活性。此外，研究了4，6-二氟-5-羟基苯基图案（9），以验证酚部分的最佳位置。化合物5b成为最有效和选择性的抑制剂。此外，进一步的分析证明了5b作为有效的抗氧化剂和山梨糖醇在离体大鼠晶状体中的抑制剂。结合以上属性，5b可以作为针对长期糖尿病并发症的先导化合物。
• A Study of the Electrophilic Aroylation of 1-Aryl-1<i>H</i>-pyrroles: An Improved Preparation of an Active and Selective Aldose Reductase Inhibitor
  作者：Nikolaos Kontonikas、Panagiota Kotsampasakou、Nikolaos Sakalis、Vassilis J. Demopoulos

  DOI：10.1080/00304948.2019.1577109

  日期：2019.3.4

  obtained with the combination of CH3CN as the solvent and KI as the catalyst (Table 1, entry 6). All compounds were isolated by flash column chromatography, and the solids were further recrystallized. Structural identification was based on spectroscopic methods (IR, NMR and HRMS). The data show that the most selective procedure for C-a substitution is the one with CH3CN and KI. Thus, we went on to investigate

  芳酰基-1-芳基-1H-吡咯部分是存在于许多生物活性化合物中的重要支架。基于这样的先例，我们被提示研究 1-苯基-1H-吡咯的亲电子苯甲酰化 (1)。我们试图开发一种合适的方法来选择性制备在未充分探索的吡咯基 Ca 位置具有芳酰基取代基的 1-芳基-1H-吡咯基衍生物。本文所述的新方法用于制备已知的活性和选择性醛糖还原酶抑制剂 (ARI) ([1,1'-联苯]-4-yl)[1-(3,5-difluoro-4-hydroxyphenyl)-1Hpyrrol -2-基]甲酮 (2)。我们之前已经制备了化合物 2，但是收率低且没有选择性。因此，在目前的工作中，我们改进了我们自己的方法论。原来，通过改变反应物的比例和添加硝基甲烷来研究 AlCl3 催化 1 与苯甲酰氯的反应（表 1，条目 1-3）。在所有情况下，主要产物是 Cb 取代的吡咯基衍生物 3。然而，我们注意到，硝基甲烷的加入导致形成少量
• Synthesis of derivatives of the keto-pyrrolyl-difluorophenol scaffold: Some structural aspects for aldose reductase inhibitory activity and selectivity
  作者：Eleni Kotsampasakou、Vassilis J. Demopoulos

  DOI：10.1016/j.bmc.2012.12.015

  日期：2013.2

  ALR1 range from 1 (in case of compound 3b) to 238 (in case of compound 3a). Finally, we found out that the presence of an additional (secondary) aromatic area is not a prerequisite feature for ARI activity.

  通过Friedel-Crafts酰化反应，通过优化和部分选择性的合成步骤，合成了7种新颖的ARI（3a – c，4a – c和5）。合成的ARI的IC 50 ALR2值范围为0.19μM（对于化合物3b而言）至2.3μM（对于化合物4a而言），而对ALR1的选择性指数的值介于1（对于化合物3b而言）至2。 238（在化合物3a的情况下）。最后，我们发现存在一个额外的（二级）芳族区域不是ARI活性的先决条件。
• Clauson–Kaas-Type Synthesis of Pyrrolyl-phenols, from the Hydrochlorides of Aminophenols, in the Presence of Nicotinamide
  作者：Maria Chatzopoulou、Eleni Kotsampasakou、Vassilis J. Demopoulos

  DOI：10.1080/00397911.2012.753460

  日期：2013.11.2

  A facile Clauson-Kaas-type pyrrolyl-phenol synthesis has been achieved in the presence of nicotinamide, which is inexpensive and nontoxic. The starting material is aminophenol hydrochloride. This is advantageous in certain cases because it is the only isolatable form of the corresponding aminophenol. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications (R) for the following free supplemental resource: Full experimental and spectral details.]
• [1-(3,5-Difluoro-4-hydroxyphenyl)-1<i>H</i>-pyrrol-3-yl]phenylmethanone as a Bioisostere of a Carboxylic Acid Aldose Reductase Inhibitor
  作者：Ioannis Nicolaou、Chariklia Zika、Vassilis J. Demopoulos

  DOI：10.1021/jm031060t

  日期：2004.5.1

  [1-(3,5-Difluoro-4-hydroxyphenyl)-1H-pyrrol-3-yl]phenylmethanone (6) was synthesized as a putative bioisostere of the known aldose reductase (AR) inhibitor (3-benzoylpyrrol-1-yl)acetic acid (I). It was found that 6 is approximately 5 times more potent as an in vitro inhibitor of AR than I, with an IC50 value in the submicromolar range. Furthermore, 6 showed considerable activity in an in vitro experimental glycation model of diabetes mellitus. Our results support the notion that 6 might become a useful lead structure.