biphenyl-4-yl(1H-pyrrol-3-yl)methanone | 220968-58-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: biphenyl-4-yl(1H-pyrrol-3-yl)methanone
• 英文别名: (4-phenylphenyl)-(1H-pyrrol-3-yl)methanone
• CAS: 220968-58-1
• 化学式: C₁₇H₁₃NO
• 分子量: 247.296
• InChiKey: ZLVBOXWSDBLSAC-UHFFFAOYSA-N

物化性质

• 沸点：
  455.5±28.0 °C(Predicted)
• 密度：
  1.171±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  32.9
• 氢给体数：
  1
• 氢受体数：
  1

反应信息

• 作为反应物：
  描述：

  biphenyl-4-yl(1H-pyrrol-3-yl)methanone 在 tris[2-(methoxyethoxy)ethyl]amine 、 sodium hydride 作用下， 以 1,4-二氧六环 、 甲苯 为溶剂， 反应 1.0h， 生成 [3-(Biphenyl-4-carbonyl)-pyrrol-1-yl]-acetic acid
  参考文献：
  名称：

  Substituted Pyrrol-1-ylacetic Acids That Combine Aldose Reductase Enzyme Inhibitory Activity and Ability To Prevent the Nonenzymatic Irreversible Modification of Proteins from Monosaccharides

  摘要：

  Starting from the known inhibitory activity of (3-benzoylpyrrol-1-yl)acetic acid (1) and (2-benzoylpyrrol-1-yl)acetic acid (II), a series of 3-aroyl and 2,4-bis-aroyl derivatives (54-75) were synthesized and tested for inhibition of aldose reductase, an enzyme involved in the appearance of diabetic complications. It was found that a number of the tested compounds exhibited considerable activity in the micromolar range. Important structural features for the potent compounds is the presence of substituents with relatively low Hammett sigma values and/ or moieties which increase their overall aromatic area. The most active derivative was the [2,4-bis(4-methoxybenzoyl)pyrrol-1-yl] acetic acid (75), with potency favorably compared to known ARIs such as tolrestat, epalrestat, zopolrestat, and fidarestat. Four selected derivatives were also evaluated for their ability to interfere with the oxidative modification of serum albumin in an in vitro experimental glycation model of diabetes mellitus. All of them showed considerable activity, comparable to the known inhibitor trolox. Our results, taken together, indicate that compound 75 combines favorably two biological activities directly connected to a number of pathological conditions related to the chronic diabetes mellitus.

  DOI：

  10.1021/jm0209477
• 作为产物：
  描述：

  在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 生成 biphenyl-4-yl(1H-pyrrol-3-yl)methanone
  参考文献：
  名称：

  1-苯磺酰基-1 H-吡咯的Friedel-crafts酰化制备3-芳酰基吡咯的研究

  摘要：

  在这项工作中，我们研究了氯化铝催化的1-苯磺酰基-1 H-吡咯与一系列11种芳酰氯的反应。形成的产物不是分离的，而是水解成目标3-芳基吡咯的总产率，通常高于50％。但是，在富含π电子的1-苯基-1 H-吡咯-3-羰基氯和1-甲基-1 H-吲哚-3-羰基氯的情况下，发生了显着的C-2取代，导致分离出相应的1-苯磺酰基-2-芳酰基吡咯作为主要或唯一产品。从1-三异丙基硅烷基-1 H-吡咯开始合成所需的C-3异构体。

  DOI：

  10.1002/jhet.5570350619

文献信息

• Enhancing activity and selectivity in a series of pyrrol-1-yl-1-hydroxypyrazole-based aldose reductase inhibitors: The case of trifluoroacetylation
  作者：Nikolaos Papastavrou、Maria Chatzopoulou、Jana Ballekova、Mario Cappiello、Roberta Moschini、Francesco Balestri、Alexandros Patsilinakos、Rino Ragno、Milan Stefek、Ioannis Nicolaou

  DOI：10.1016/j.ejmech.2017.02.053

  日期：2017.4

  established as a bioisostere of acetic acid in a group of aroyl-substituted pyrrolyl derivatives. In the present work, optimization of this new class of ARIs was achieved by the addition of a trifluoroacetyl group on the pyrrole ring. Eight novel compounds were synthesized and tested for their inhibitory activity towards ALR2 and selectivity against aldehyde reductase (ALR1). All compounds proved potent

  40多年来，醛糖还原酶（ALR2）一直是治疗干预的目标。首先，由于其在长期糖尿病并发症中的作用，最近成为炎症和癌症的关键介质。但是，制备小分子醛糖还原酶抑制剂（ARIs）的努力大多产生了药代动力学较差的羧酸。为了解决该限制，先前已将1-羟基吡唑部分确立为一组芳酰基取代的吡咯基衍生物中的乙酸的生物等排体。在目前的工作中，通过在吡咯环上添加三氟乙酰基可以实现对这类新型ARI的优化。合成了八种新化合物，并测试了它们对ALR2的抑制活性和对醛还原酶（ALR1）的选择性。所有化合物被证明是ALR2的有效和选择性抑制剂（IC 50 / ALR 2 ＝0.043-0.242μM，选择性指数＝ 190-858），同时保留了良好的理化特性。进一步评估了活性最高的（4g）和选择性（4d）化合物在离体大鼠晶状体中抑制山梨糖醇形成并表现出底物特异性抑制的能力。
• 1-Hydroxypyrazole as a bioisostere of the acetic acid moiety in a series of aldose reductase inhibitors
  作者：Nikolaos Papastavrou、Maria Chatzopoulou、Kyriaki Pegklidou、Ioannis Nicolaou

  DOI：10.1016/j.bmc.2013.06.062

  日期：2013.9

  Therapeutic intervention with aldose reductase inhibitors appears to be promising for major pathological conditions (i.e., long-term diabetic complications and inflammatory pathologies). So far, however, clinical candidates have failed due to adverse side-effects (spiroimides) or poor bioavailability (carboxylic acids). In this work, we succeeded in the bioisosteric replacement of an acetic acid moiety with that of 1-hydroxypyrazole. This new scaffold appears to have a superior physicochemical profile, while attaining inhibitory activity in the submicromolar range. (C) 2013 Elsevier Ltd. All rights reserved.
• Substituted Pyrrol-1-ylacetic Acids That Combine Aldose Reductase Enzyme Inhibitory Activity and Ability To Prevent the Nonenzymatic Irreversible Modification of Proteins from Monosaccharides
  作者：Ioannis Nicolaou、Vassilis J. Demopoulos

  DOI：10.1021/jm0209477

  日期：2003.1.1

  Starting from the known inhibitory activity of (3-benzoylpyrrol-1-yl)acetic acid (1) and (2-benzoylpyrrol-1-yl)acetic acid (II), a series of 3-aroyl and 2,4-bis-aroyl derivatives (54-75) were synthesized and tested for inhibition of aldose reductase, an enzyme involved in the appearance of diabetic complications. It was found that a number of the tested compounds exhibited considerable activity in the micromolar range. Important structural features for the potent compounds is the presence of substituents with relatively low Hammett sigma values and/ or moieties which increase their overall aromatic area. The most active derivative was the [2,4-bis(4-methoxybenzoyl)pyrrol-1-yl] acetic acid (75), with potency favorably compared to known ARIs such as tolrestat, epalrestat, zopolrestat, and fidarestat. Four selected derivatives were also evaluated for their ability to interfere with the oxidative modification of serum albumin in an in vitro experimental glycation model of diabetes mellitus. All of them showed considerable activity, comparable to the known inhibitor trolox. Our results, taken together, indicate that compound 75 combines favorably two biological activities directly connected to a number of pathological conditions related to the chronic diabetes mellitus.
• A study of the friedel-crafts acylation of 1-benzenesulfonyl-1<i>H</i>-pyrrole in the preparation of 3-aroylpyrroles
  作者：Ioannis Nicolaou、Vassilis J. Demopoulos

  DOI：10.1002/jhet.5570350619

  日期：1998.11

  In this work, we studied the aluminum chloride catalyzed reaction of 1-benzenesulfonyl-1H-pyrrole with a series of eleven aroyl chlorides. The products formed were not isolated, but hydrolyzed to the target 3-aroylpyrroles in overall yields, usually, higher than 50%. However, in the cases with the π electron rich 1-phenyl-1H-pyrrole-3-carbonyl chloride and 1-methyl-1H-indole-3-carbonyl chloride significant

  在这项工作中，我们研究了氯化铝催化的1-苯磺酰基-1 H-吡咯与一系列11种芳酰氯的反应。形成的产物不是分离的，而是水解成目标3-芳基吡咯的总产率，通常高于50％。但是，在富含π电子的1-苯基-1 H-吡咯-3-羰基氯和1-甲基-1 H-吲哚-3-羰基氯的情况下，发生了显着的C-2取代，导致分离出相应的1-苯磺酰基-2-芳酰基吡咯作为主要或唯一产品。从1-三异丙基硅烷基-1 H-吡咯开始合成所需的C-3异构体。