2-chloro-1-methoxy-4-(2-nitrovinyl)benzene | 58776-06-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-chloro-1-methoxy-4-(2-nitrovinyl)benzene
• 英文别名: 3-Chlor-4-methoxy-β-nitrostyrol；3-chloro-4-methoxy-β-nitrostyrene；2-chloro-1-methoxy-4-(2-nitroethenyl)benzene
• CAS: 58776-06-0
• 化学式: C₉H₈ClNO₃
• mdl: MFCD21135245
• 分子量: 213.62
• InChiKey: XAEBQJANFSJNOD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  14
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.111
• 拓扑面积：
  55
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-chloro-1-methoxy-4-(2-nitrovinyl)benzene 在 lithium aluminium tetrahydride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 乙醚 、 二氯甲烷 、 水 为溶剂， 反应 5.0h， 生成 N-(3-chloro-4-methoxyphenylethyl)-β-(3'-methoxyphenyl)acetamide
  参考文献：
  名称：

  2,3,9- and 2,3,11-Trisubstituted tetrahydroprotoberberines as D2 dopaminergic ligands

  摘要：

  Dopamine-mediated neurotransmission plays an important role in relevant psychiatric and neurological disorders. Nowadays, there is an enormous interest in the development of new dopamine receptors (DR) acting drugs as potential new targets for the treatment of schizophrenia or Parkinson's disease. Previous studies have revealed that isoquinoline compounds such as tetrahydroisoquinolines (THIQs) and tetrahydroprotoberberines (THPBs) can behave as selective D-2 dopaminergic alkaloids since they share structural similarities with dopamine. In the present study we have synthesized eleven 2,3,9- and 2,3,11-trisubstituted THPB compounds (six of them are described for the first time) and evaluated their potential dopaminergic activity. Binding studies on rat striatal membranes were used to evaluate their affinity and selectivity towards D-1 and D-2 DR and establish the structure activity relationship (SAR) as dopaminergic agents. In general, all the tested THPBs with protected phenolic hydroxyls showed a lower affinity for D-1 and D-2 DR than their corresponding homologues with free hydroxyl groups. In previous studies in which dopaminergic affinity of 1-benzyl-THIQs (BTHIQs) was evaluated, the presence of a Cl into the A-ring resulted in increased affinity and selectivity towards D-2 DR. This is in contrast with the current study since the existence of a chlorine atom into the A-ring of the THPBs caused increased affinity for D-1 DR but dramatically reduced the selectivity for D-2 DR. An OH group in position 9 of the THPB (9f) resulted in a higher affinity for DR than its homologue with an OH group in position 11 (9e) (250 fold for D-2 DR). None of the compounds showed any cytotoxicity in freshly isolated human neutrophils. A molecular modelling study of three representative THPBs was carried out. The combination of MD simulations with DFT calculations provided a clear picture of the ligand binding interactions from a structural and energetic point of view. Therefore, it is likely that compound 9d (2,3,9-trihydroxy-THPB) behave as D-2 DR agonist since serine residues cluster are crucial for agonist binding and receptor activation. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.07.036
• 作为产物：
  描述：

  4-甲氧基苯甲醛 在 磺酰氯 、 ammonium acetate 、 溶剂黄146 作用下， 反应 4.0h， 生成 2-chloro-1-methoxy-4-(2-nitrovinyl)benzene
  参考文献：
  名称：

  Shedding Light on the D₁‐Like Receptors: A Fluorescence‐Based Toolbox for Visualization of the D₁ and D₅ Receptors**

  摘要：

  摘要多巴胺 D1 样受体是中枢神经系统中最丰富的多巴胺受体类型，即使在发现了几十年之后，仍然对神经系统疾病的研究具有极大的兴趣。我们在本文中描述了一组新的荧光配体的合成，这些配体在结构上源自 D1R 拮抗剂 SCH-23390，并用两种不同的荧光染料标记，是 D1 样受体可视化的工具化合物。在放射性配体结合研究中进行的药理学表征发现，UR-NR435 (25) 是 D1 类受体的高亲和性配体（pKi (D1R)=8.34, pKi (D5R)=7.62 ），对 D2 类受体具有极佳的选择性。在 Gs 异源三聚体解离试验中，化合物 25 被证明是 D1R 和 D5R 的中性拮抗剂，这是在使用全细胞时避免受体内化和降解的一个重要特征。在使用共聚焦显微镜进行的动力学结合研究中，中性拮抗剂 25 显示出与 D1R 的快速结合和完全解离，这验证了它在荧光显微镜下的适用性。此外，分子亮度研究确定了该配体个位数纳摩尔的结合亲和力，这与放射性配体的结合数据非常吻合。因此，这种荧光配体是在各种实验装置中对原生 D1 受体进行精密表征的有用工具。

  DOI：

  10.1002/cbic.202300658

文献信息

• Tetrahydroisoquinolines as dopaminergic ligands: 1-Butyl-7-chloro-6-hydroxy-tetrahydroisoquinoline, a new compound with antidepressant-like activity in mice
  作者：Inmaculada Berenguer、Noureddine El Aouad、Sebastián Andujar、Vanessa Romero、Fernando Suvire、Thomas Freret、Almudena Bermejo、María Dolores Ivorra、Ricardo D. Enriz、Michel Boulouard、Nuria Cabedo、Diego Cortes

  DOI：10.1016/j.bmc.2009.05.079

  日期：2009.7

  1-position on the affinity for dopamine receptors. All the compounds displayed affinity for D1-like and/or D2-like dopamine receptors in striatal membranes, and were unable to inhibit [3H]-dopamine uptake in striatal synaptosomes. Different structure requirements have been observed for adequate D1 or D2 affinities. This paper details the synthesis, structural elucidation, dopaminergic binding assays, structure–activity

  制备了三个系列的1-取代-7-氯-6-羟基-四氢异喹啉（1-丁基-，1-苯基-和1-苄基衍生物），以研究这些基团在1位上的每个基团对羟基的影响。对多巴胺受体的亲和力。所有化合物均显示出对纹状体膜中D 1类和/或D 2类多巴胺受体的亲和力，并且不能抑制纹状体突触体中的[ 3 H]-多巴胺摄取。对于足够的D 1或D 2已观察到不同的结构要求亲和力。本文详细介绍了这三个系列的异喹啉的合成，结构解析，多巴胺能结合测定，结构-活性关系（SAR）。此外，对D 2样受体的亲和力最高的1-丁基-7-氯-6-羟基四氢异喹啉（1e）（K i值为66 nM）和最高的选择性（49倍D 2对D 1）然后通过体外结合实验在小鼠的行为分析（自发活动和强迫游泳测试）中对其进行评估。化合物1e在大剂量范围内（0.04–25 mg / kg）增加运动能力。此外，在强制游泳试验中，该先导化合物以不改变运动活性的剂量（0.01 mg
• Synthesis of new antimicrobial pyrrolo[2,1-a]isoquinolin-3-ones
  作者：Laura Moreno、Javier Párraga、Abraham Galán、Nuria Cabedo、Jaime Primo、Diego Cortes

  DOI：10.1016/j.bmc.2012.09.033

  日期：2012.11

  The attractive structure of the pyrroloisoquinoline moiety, together with its potential antimicrobial activity, encouraged us to prepare six 8-substituted and seven 8,9-disubstituted-1,2,3,5,6,10b-hexahydropyrrolo[2,1-a]isoquinolin-3-ones in a few steps with good yields. We applied a convenient methodology via double intramolecular cyclization conducted by a Bischler-Napieralski cyclodehydration-imine reduction sequence, which is widely employed in the synthesis of isoquinoline alkaloids. Therefore, we synthesized three series of these pyrrolo[2,1-a]isoquinolin-3-ones characterized by the substituent at the 8-position or 8,9-positions of the aromatic ring: (a) different side chains are attached to an 8-OH group (series 1); (b) a chlorine atom is attached to the 8-position (series 2); and (c) 8- and 9-carbons are bearing an identical group (series 3). The compounds bearing a benzylic moiety at the 8-position, for example, 8-benzyloxy-pyrrolo[2,1-a]isoquinolin-3-one (1a) and 8-(4-fluorobenzyloxy)-pyrrolo[2,1-a]isoquinolin-3-one (1e), as well as, a 8-chloro-9-methoxy moiety including the 8-chloro-9-methoxy-pyrrolo[2,1-a]isoquinolin-3-one (2a), provided the most fungicide and bactericide agents, respectively. (C) 2012 Elsevier Ltd. All rights reserved.
• 2,3,9- and 2,3,11-Trisubstituted tetrahydroprotoberberines as D2 dopaminergic ligands
  作者：Javier Párraga、Nuria Cabedo、Sebastián Andujar、Laura Piqueras、Laura Moreno、Abraham Galán、Emilio Angelina、Ricardo D. Enriz、María Dolores Ivorra、María Jesús Sanz、Diego Cortes

  DOI：10.1016/j.ejmech.2013.07.036

  日期：2013.10

  Dopamine-mediated neurotransmission plays an important role in relevant psychiatric and neurological disorders. Nowadays, there is an enormous interest in the development of new dopamine receptors (DR) acting drugs as potential new targets for the treatment of schizophrenia or Parkinson's disease. Previous studies have revealed that isoquinoline compounds such as tetrahydroisoquinolines (THIQs) and tetrahydroprotoberberines (THPBs) can behave as selective D-2 dopaminergic alkaloids since they share structural similarities with dopamine. In the present study we have synthesized eleven 2,3,9- and 2,3,11-trisubstituted THPB compounds (six of them are described for the first time) and evaluated their potential dopaminergic activity. Binding studies on rat striatal membranes were used to evaluate their affinity and selectivity towards D-1 and D-2 DR and establish the structure activity relationship (SAR) as dopaminergic agents. In general, all the tested THPBs with protected phenolic hydroxyls showed a lower affinity for D-1 and D-2 DR than their corresponding homologues with free hydroxyl groups. In previous studies in which dopaminergic affinity of 1-benzyl-THIQs (BTHIQs) was evaluated, the presence of a Cl into the A-ring resulted in increased affinity and selectivity towards D-2 DR. This is in contrast with the current study since the existence of a chlorine atom into the A-ring of the THPBs caused increased affinity for D-1 DR but dramatically reduced the selectivity for D-2 DR. An OH group in position 9 of the THPB (9f) resulted in a higher affinity for DR than its homologue with an OH group in position 11 (9e) (250 fold for D-2 DR). None of the compounds showed any cytotoxicity in freshly isolated human neutrophils. A molecular modelling study of three representative THPBs was carried out. The combination of MD simulations with DFT calculations provided a clear picture of the ligand binding interactions from a structural and energetic point of view. Therefore, it is likely that compound 9d (2,3,9-trihydroxy-THPB) behave as D-2 DR agonist since serine residues cluster are crucial for agonist binding and receptor activation. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Shedding Light on the D₁‐Like Receptors: A Fluorescence‐Based Toolbox for Visualization of the D₁ and D₅ Receptors**
  作者：Niklas Rosier、Denise Mönnich、Martin Nagl、Hannes Schihada、Alexei Sirbu、Nergis Konar、Irene Reyes‐Resina、Gemma Navarro、Rafael Franco、Peter Kolb、Paolo Annibale、Steffen Pockes

  DOI：10.1002/cbic.202300658

  日期：2024.1.15

  Dopamine D₁‐like receptors are the most abundant type of dopamine receptors in the central nervous system and, even after decades of discovery, still highly interesting for the study of neurological diseases. We herein describe the synthesis of a new set of fluorescent ligands, structurally derived from D₁R antagonist SCH‐23390 and labeled with two different fluorescent dyes, as tool compounds for the visualization of D₁‐like receptors. Pharmacological characterization in radioligand binding studies identified UR‐NR435 (25) as a high‐affinity ligand for D₁‐like receptors (pK_i (D₁R)=8.34, pK_i (D₅R)=7.62) with excellent selectivity towards D₂‐like receptors. Compound 25 proved to be a neutral antagonist at the D₁R and D₅R in a G_s heterotrimer dissociation assay, an important feature to avoid receptor internalization and degradation when working with whole cells. The neutral antagonist 25 displayed rapid association and complete dissociation to the D₁R in kinetic binding studies using confocal microscopy verifying its applicability for fluorescence microscopy. Moreover, molecular brightness studies determined a single‐digit nanomolar binding affinity of the ligand, which was in good agreement with radioligand binding data. For this reason, this fluorescent ligand is a useful tool for a sophisticated characterization of native D₁ receptors in a variety of experimental setups.

  摘要多巴胺 D1 样受体是中枢神经系统中最丰富的多巴胺受体类型，即使在发现了几十年之后，仍然对神经系统疾病的研究具有极大的兴趣。我们在本文中描述了一组新的荧光配体的合成，这些配体在结构上源自 D1R 拮抗剂 SCH-23390，并用两种不同的荧光染料标记，是 D1 样受体可视化的工具化合物。在放射性配体结合研究中进行的药理学表征发现，UR-NR435 (25) 是 D1 类受体的高亲和性配体（pKi (D1R)=8.34, pKi (D5R)=7.62 ），对 D2 类受体具有极佳的选择性。在 Gs 异源三聚体解离试验中，化合物 25 被证明是 D1R 和 D5R 的中性拮抗剂，这是在使用全细胞时避免受体内化和降解的一个重要特征。在使用共聚焦显微镜进行的动力学结合研究中，中性拮抗剂 25 显示出与 D1R 的快速结合和完全解离，这验证了它在荧光显微镜下的适用性。此外，分子亮度研究确定了该配体个位数纳摩尔的结合亲和力，这与放射性配体的结合数据非常吻合。因此，这种荧光配体是在各种实验装置中对原生 D1 受体进行精密表征的有用工具。