1-(3-氯-4-氟苯基)-吡咯-2,5-二酮 | 134220-37-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯啉
• 中文名称: 1-(3-氯-4-氟苯基)-吡咯-2,5-二酮
• 中文别名: 1-(3-氯-4-氟苯基)-2,5-二氢-1H-吡咯-2,5-二酮；1-(3-氯-4-氟苯基)-1H-吡咯-2,5-二酮
• 英文名称: 1-(3-chloro-4-fluorophenyl)-1H-pyrrole-2,5-dione
• 英文别名: N-(3-chloro-4-fluorophenyl)maleimide；1-(3-chloro-4-fluorophenyl)pyrrole-2,5-dione
• CAS: 134220-37-4
• 化学式: C₁₀H₅ClFNO₂
• mdl: MFCD00176541
• 分子量: 225.607
• InChiKey: MALVOABWAGKNIK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  15
• 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：
  37.4
• 氢给体数：
  0
• 氢受体数：
  3

安全信息

• 危险等级：
  IRRITANT

反应信息

• 作为反应物：
  描述：

  1-(3-氯-4-氟苯基)-吡咯-2,5-二酮 在 吡啶 、 氯化亚砜 作用下， 以 二氯甲烷 为溶剂， 反应 3.25h， 生成 3-chloro-1-(3-chloro-4-fluorophenyl)-4-morpholino-1H-pyrrole-2,5-dione
  参考文献：
  名称：

  An Optimized RAD51 Inhibitor That Disrupts Homologous Recombination without Requiring Michael Acceptor Reactivity

  摘要：

  Homologous recombination (HR) is an essential process in cells that provides repair of DNA double-strand breaks and lesions that block DNA replication. RAD51 is an evolutionarily conserved protein that is central to HR. Overexpression of RAD51 protein is common in cancer cells and represents a potential therapeutic target in oncology. We previously described a chemical inhibitor of RAD51, called RI-1 (referred to as compound 1 in this report). The chloromaleimide group of this compound is thought to act as a Michael acceptor and react with the thiol group on C319 of RAD51, using a conjugate addition-elimination mechanism. In order to reduce the likelihood of off-target effects and to improve compound stability in biological systems, we developed an analogue of compound 1 that lacks maleimide-based reactivity but retains RAD51 inhibitory activity. This compound, 1-(3,4-dichlorophenyl)-3-(4-methoxyphenyl)-4-morpholino-1H-pyrrole-2,5-dione, named RI-2 (referred to as compound 7a in this report), appears to bind reversibly to the same site on the RAD51 protein as does compound 1. Like compound 1, compound 7a specifically inhibits HR repair in human cells.

  DOI：

  10.1021/jm301565b
• 作为产物：
  描述：

  4-(3-Chloro-4-fluoroanilino)-4-oxobut-2-enoic acid 在 sodium acetate 作用下， 以 乙酸酐 为溶剂， 反应 0.5h， 生成 1-(3-氯-4-氟苯基)-吡咯-2,5-二酮
  参考文献：
  名称：

  通过虚拟筛选结合生物学评估，发现，设计和合成2型腺苷酸环化酶有效激动剂。

  摘要：

  腺苷酸环化酶（AC）在三磷酸腺苷（ATP）转化为第二信使环单磷酸腺苷（cAMP）的过程中起关键作用。研究表明2型腺苷酸环化酶（AC2）是许多疾病的潜在药物靶标，但是，到目前为止，尚无AC2选择性激动剂的报道。在这项研究中，已经进行了基于对接的虚拟筛选与基于细胞的生物学检测相结合，以发现新型有效的和选择性的AC2激动剂。虚拟筛选揭示了一种新型的命中化合物8，作为AC2激动剂，在重组人hAC2 + HEK293细胞上的EC50值为8.10μM。在重组AC2细胞上进一步研究了基于化合物8衍生物的SAR（结构活性关系），发现化合物73是最具活性的激动剂，EC50为90 nM，它比报道的激动剂福斯高林强160倍，并且可以选择性激活AC2以抑制白介素6的表达。新型AC2选择性激动剂的发现将为研究AC2的生理功能提供一种新颖的化学探针。

  DOI：

  10.1016/j.ejmech.2020.112115

文献信息

• Pyridinium -toluenesulfonylmethylide as a formyl anion equivalent
  作者：Rudolph A. Abramovitch、Suchet S. Mathur、Daniel W. Saunders、Danny P. Vanderpool

  DOI：10.1016/s0040-4039(00)71451-1

  日期：1980.1

  Pyridinium -toluenesulfonylmethylide serves as a formyl anion equivalent and, in the presence of an alcohol, undergoes 1,4-addition to -substituted maleimides to give alkoxy- (or aryloxy)-methylene-succinimides. The protected aldehyde group can be liberated readily.

  吡啶鎓-甲苯磺酰亚甲基用作甲酰基阴离子当量，并且在醇的存在下，对取代的马来酰亚胺进行1,4-加成，得到烷氧基-（或芳氧基）-亚甲基-琥珀酰亚胺。被保护的醛基可以容易地释放。
• Ruthenium(II)-Catalyzed Hydroarylation of Maleimides Using Carboxylic Acids as a Traceless Directing Group
  作者：Anup Mandal、Harekrishna Sahoo、Suman Dana、Mahiuddin Baidya

  DOI：10.1021/acs.orglett.7b01964

  日期：2017.8.4

  ready-stock aryl carboxylic acids has been developed based on weak carboxylate-directed ortho-C–H alkylation and concomitant decarboxylation processes, fabricating 3-aryl succinimides, a recurrent scaffold in drug molecules, in high yields (up to 97%). The protocol features operational simplicity, avoids the need for precious metal additives/oxidants, and offers broad substrate scope with formal meta- and

  基于弱羧酸盐定向的邻-C-H烷基化和伴随的脱羧过程，开发了一种高效的Ru（II）催化的马来酰亚胺与现成的芳基羧酸进行加氢芳基化反应，制备了3-芳基琥珀酰亚胺，这是药物分子中的常见骨架，高产（高达97％）。该协议具有操作简单，无需贵金属添加剂/氧化剂的特点，并提供了具有正式的间位和对位选择性的广泛底物范围。它代表了Ru（II）催化马来酰亚胺与无偏苯甲酸直接芳基化的第一个例子。
• Rh(<scp>iii</scp>)-Catalyzed cascade annulation to produce an <i>N</i>-acetyl chain of spiropyrroloisoquinoline derivatives
  作者：Yuan He、Jing Zheng、Lin Dong

  DOI：10.1039/d2ob00137c

  日期：——

  A new rhodium(III)-catalyzed multistep cascade spirocyclization approach was developed to synthesize a novel N-acetyl chain of spiropyrroloisoquinoline derivatives using oxadiazoles as the directing group. This one-pot reaction also isolates aryloxadiazole derivatives as cross-coupling intermediates. This simple approach could efficiently expand the scope of the skeletons of isoquinolines and aryloxadiazoles

  开发了一种新的铑( III )催化多步级联螺环化方法，以恶二唑为导向基团合成新型螺吡咯并异喹啉衍生物的N-乙酰链。这种一锅法反应还分离出芳基恶二唑衍生物作为交叉偶联中间体。这种简单的方法可以有效地扩大异喹啉和芳基恶二唑骨架的范围。
• Bicyclic α-Iminophosphonates as High Affinity Imidazoline I₂ Receptor Ligands for Alzheimer’s Disease
  作者：Sònia Abás、Sergio Rodríguez-Arévalo、Andrea Bagán、Christian Griñán-Ferré、Foteini Vasilopoulou、Iria Brocos-Mosquera、Carolina Muguruza、Belén Pérez、Elies Molins、F. Javier Luque、Pilar Pérez-Lozano、Steven de Jonghe、Dirk Daelemans、Lieve Naesens、José Brea、M. Isabel Loza、Elena Hernández-Hernández、Jesús A. García-Sevilla、M. Julia García-Fuster、Milica Radan、Teodora Djikic、Katarina Nikolic、Mercè Pallàs、Luis F. Callado、Carmen Escolano

  DOI：10.1021/acs.jmedchem.9b02080

  日期：2020.4.9

  Imidazoline I2 receptors (I2-IR), widely distributed in the CNS and altered in patients that suffer from neurodegenerative disorders, are orphans from a structural point of view, and new I2-IR ligands are urgently required for improving their pharmacological characterization. We report the synthesis and three-dimensional quantitative structure–activity relationship (3D-QSAR) studies of a new family

  从结构的观点来看，咪唑啉I 2受体（I 2 -IR）广泛分布在中枢神经系统中，并在患有神经退行性疾病的患者中发生改变，从结构的角度来看是孤儿，迫切需要新的I 2 -IR配体来改善其药理特性。我们报告的合成和三维定量结构-活性关系（3D-QSAR）研究的双环的α-亚氨基膦酸酯的新家族，具有与人脑I 2 -IR相关的亲和力。用选定化合物对小鼠进行的急性治疗可显着降低海马Fas相关蛋白的死亡域（FADD），这是神经保护作用的关键信号传递介质。此外，体内对家族性阿尔茨海默氏病5xFAD小鼠模型的研究表明，它在行为和认知方面具有有益作用。这些结果得到与认知下降和阿尔茨海默氏病相关的分子途径变化的支持。因此，双环α-亚氨基膦酸酯是可以为I 2 -IR，特别是对于未满足的神经退行性疾病开辟新的治疗途径的工具。
• [EN] METHODS AND COMPOSITIONS INVOLVING RAD51 INHIBITORS<br/>[FR] PROCÉDÉS ET COMPOSITIONS IMPLIQUANT DES INHIBITEURS DE RAD51
  申请人：UNIV CHICAGO

  公开号：WO2014085545A1

  公开（公告）日：2014-06-05

  The present invention concerns methods and compositions involving inhibitors and of RAD51, a protein involved in homologous recombination. In some embodiments, there are methods for sensitizing cells to the effects of DNA damaging agents, which can have particular applications for cancer patients. In some embodiments of the invention, the RAD51 inhibitor is a small molecule that directly affects RAD51 activity, such as its ability to promote filament formation.

  本发明涉及涉及RAD51抑制剂和RAD51的方法和组合物，RAD51是参与同源重组的蛋白质。在某些实施例中，有一些方法可以使细胞对DNA损伤剂的影响变得更敏感，这对癌症患者可能具有特殊应用。在本发明的某些实施例中，RAD51抑制剂是一种直接影响RAD51活性的小分子，例如其促进丝状物形成的能力。