2-([1,1'-biphenyl]-4-ylmethylene)-1H-indene-1,3(2H)-dione | 18913-75-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: 2-([1,1'-biphenyl]-4-ylmethylene)-1H-indene-1,3(2H)-dione
• 英文别名: 2-(biphenyl-4-ylmethylene)-1H-inden-1,3[2H]-dione；2-(biphenyl-4-yl-methyliden)-indan-1,3-dione；2-(4'-Biphenylmethylen)-1,3-indandion；2-(4-Phenylbenzyliden)-1,3-indandion；2-[(4-Phenylphenyl)methylidene]indene-1,3-dione
• CAS: 18913-75-2
• 化学式: C₂₂H₁₄O₂
• 分子量: 310.352
• InChiKey: YIDOGHAZYODHEB-UHFFFAOYSA-N

物化性质

• 沸点：
  536.2±50.0 °C(Predicted)
• 密度：
  1.268±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  34.1
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-([1,1'-biphenyl]-4-ylmethylene)-1H-indene-1,3(2H)-dione 、 3-氨基-5,5-二甲基-2-环己烯-1-酮 在 溶剂黄146 作用下， 反应 0.05h， 以67%的产率得到11-(biphenyl-4-yl)-3,3-dimethyl-1,2,3,4,5,11-hexahydroindeno[1,2-b]quinoline-1,10-dione
  参考文献：
  名称：

  Design, synthesis and 3D-QSAR studies of novel 1,4-dihydropyridines as TGFβ/Smad inhibitors

  摘要：

  Targeting TGF beta/Smad signaling is an attractive strategy for several therapeutic applications given its role as a key player in many pathologies, including cancer, autoimmune diseases and fibrosis. The class of b-annelated 1,4-dihydropyridines (DHPs) represents promising novel pharmacological tools as they interfere with this pathway in a novel fashion, i.e. through induction of TGF beta receptor type II degradation. In the present work, >40 rationally designed, novel DHPs were synthesized and evaluated for TGF beta inhibition, substantially expanding the current understanding of the SAR profile. Key findings include that the 2-position tolerates a wide variety of polar functionalities, suggesting that this region could possibly be solvent-exposed within the (thus far) unknown cellular target. A structural explanation for pathway selectivity is provided based on a diverse series of 4"-substituted DHPs, including molecular electrostatic potential (MEP) calculations. Moreover, the absolute configuration for the chiral 4-position was determined by X-ray crystal analysis and revealed that the bioactive (+)-enantiomers are (R)configured. Another key objective was to establish a 3D-QSAR model which turned out to be robust (r(2) = 0.93) with a good predictive power (r(pred)(2) = 0.69). This data further reinforces the hypothesis that this type of DHPs exerts its novel TGF beta inhibitory mode of action through binding a distinct target and that unspecific activities that would derive from intrinsic properties of the ligands (e.g., lipophilicity) play a negligible role. Therefore, the present study provides a solid basis for further ligand-based design of additional analogs or DHP scaffold-derived compounds for hit-to-lead optimization, required for more comprehensive pharmacological studies in vivo. (C) 2015 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2015.03.027
• 作为产物：
  描述：

  1,3-茚满二酮 、 对苯基苯甲醛 在 硫酸 、 溶剂黄146 作用下， 生成 2-([1,1'-biphenyl]-4-ylmethylene)-1H-indene-1,3(2H)-dione
  参考文献：
  名称：

  芬布芬，一种新型的消炎镇痛药：类似物的合成与构效关系。

  摘要：

  制备了一百个芬布芬类似物，并使用角叉菜胶，多关节炎和紫外线红斑抗炎试验以及2-苯基-1,4-苯醌扭转和发炎的爪压镇痛试验进行了测试。只有三个保留了与芬布芬相同的全范围活性：dl-4-（4-联苯基）-4-羟基丁酸，dl-4-（4-联苯基）-1,4-丁二醇和4-联苯乙酸。在这五项测试中，芬布芬的活性谱与阿司匹林，苯基丁a和消炎痛相同。此外，剂量反应衍生的药效在所有五个试验中均显示出芬布芬比阿司匹林更有效，并且至少与苯基丁a同样有效。两种相关化合物通常相似。

  DOI：

  10.1002/jps.2600660403

文献信息

• Three-Component Suzuki–Knoevenagel Synthesis of Merocyanine Libraries and Correlation Analyses of Their Oxidation Potentials and Optical Band Gaps
  作者：Tim Meyer、Roxanne Krug、Thomas J. J. Müller

  DOI：10.3390/molecules26175149

  日期：——

  The Suzuki coupling Knoevenagel condensation one-pot synthesis of boronic acids/esters, (hetero)aromatic bromo aldehydes and methylene active compounds is a highly practical consecutive three-component process to provide substance libraries with 60 donor-π-bridge-acceptor molecules, i.e., merocyanines in a broader sense, in moderate to excellent yield. As already seen with the naked eye, a broad variation

  Suzuki 偶联 Knoevenagel 缩合一锅法合成硼酸/酯、（杂）芳族溴醛和亚甲基活性化合物是一种非常实用的连续三组分工艺，可提供具有 60 个供体-π-桥-受体分子的物质库，即，更广泛意义上的部花青，产量中等至极好。正如肉眼所见，使用这种实用的合成工具可以实现光学特性的广泛变化。更系统地，在绘制光学带隙与近亲系列氧化还原活性系统的第一氧化电位时的相关性分析提供了线性相关性，并且通过扩展，两个参数图（氧化电位和发射最大值）与光学带隙平面相关性。
• Rapid and selective synthesis of spiropyrazolines and pyrazolylphthalides employing Seyferth–Gilbert reagent
  作者：Ashis Kumar Gupta、Narendra Kumar Vaishanv、Ruchir Kant、Kishor Mohanan

  DOI：10.1039/c7ob01417a

  日期：——

  diazomethylphosphonate leading to the formation of two different types of products is reported. The reaction carried out in acetone in the presence of catalytic amount of cesium fluoride afforded spiropyrazoline phosphonates via 1,3-dipolar cycloaddition reaction, whereas the reaction in methanol yielded an interesting class of pyrazolylphthalides. This strategy provides an efficient alternative method

  据报道，在2-芳亚烷基茚满-1,3-二酮与重氮二甲基膦酸二甲酯的反应中，出乎意料的产物选择性导致形成两种不同类型的产物。该反应在催化量的氟化铯的存在下在丙酮中进行，经由1，3-偶极环加成反应提供了螺吡唑啉膦酸酯，而在甲醇中的反应产生了有趣的一类吡唑基邻苯二甲酸酯。该策略为构建吡唑基邻苯二甲酰亚胺提供了一种有效的替代方法，而且该方法是通用的，可在温和的条件下运行，并且具有很高的官能团相容性。
• A Chemical Disruptor of the ClpX Chaperone Complex Attenuates the Virulence of Multidrug-Resistant <i>Staphylococcus aureus</i>
  作者：Christian Fetzer、Vadim S. Korotkov、Robert Thänert、Kyu Myung Lee、Martin Neuenschwander、Jens Peter von Kries、Eva Medina、Stephan A. Sieber

  DOI：10.1002/anie.201708454

  日期：2017.12.4

  production, which was quantified with a customized MS‐based assay platform. Transcriptome and whole‐proteome studies further confirmed the global reduction of virulence and revealed characteristic signatures of protein expression in the compound‐treated cells. Although these partially matched the pattern of ClpX knockout cells, further depletion of toxins was observed, leading to the intriguing perspective that

  的金黄色葡萄球菌ClpXP蛋白酶是细胞稳态和毒力的重要调节剂。我们使用了针对ClpXP复合物的高通量筛选，并鉴定了破坏其低聚状态的ClpX分子伴侣的特异性抑制剂。34种衍生物的合成表明该分子支架对于多样化具有限制性，仅容许微小的变化。随后对最具活性的化合物进行分析，结果显示金黄色葡萄球菌的强烈衰减毒素的产生，通过定制的基于MS的测定平台进行定量。转录组和全蛋白质组研究进一步证实了毒力的整体降低，并揭示了化合物处理细胞中蛋白质表达的特征性特征。尽管这些与ClpX基因敲除细胞的模式部分匹配，但仍观察到毒素的进一步消耗，这引起了人们的兴趣，即小分子可能直接或间接地解决了额外的毒力途径。
• [EN] CLPX INHIBITORY COMPOUNDS FOR THE TREATMENT OF MULTI RESISTANT STAPHYLOCOCCUS AUREUS VIRULENCE AND FOR THE TREATMENT OF LEUKEMIA<br/>[FR] COMPOSÉS INHIBITEURS DE CLPX POUR LE TRAITEMENT DE LA VIRULENCE DE STAPHYLOCOCCUS AUREUS MULTIRÉSISTANT ET POUR LE TRAITEMENT DE LA LEUCÉMIE
  申请人：UNIV MUENCHEN TECH

  公开号：WO2018114965A1

  公开（公告）日：2018-06-28

  The present invention relates to antibiotic compounds and their use as ClpX inhibitors and in the treatment of bacterial infections, such as infections with multi-resistant Staphylococcus aureas, and in the treatment of leukemia. The present invention further relates to respective methods of treatment.

  本发明涉及抗生素化合物及其作为ClpX抑制剂的用途，用于治疗细菌感染，如具有多重耐药性的金黄色葡萄球菌感染，以及用于治疗白血病。本发明还涉及相应的治疗方法。
• Highly Regio- and Chemoselective Palladium-Catalyzed Propargylallylation of Activated Olefins:  A Novel Route to 1,7-Enyne Derivatives
  作者：Masilamani Jeganmohan、Muthian Shanmugasundaram、Chien-Hong Cheng

  DOI：10.1021/jo0496998

  日期：2004.6.1

  assembling of activated olefins, allylic chlorides, and allenylstannanes is described. Substituted arylethylidene malononitriles 1a−g (RCHC(CN)2: R = C6H5 (1a), p-ClC6H4 (1b), p-OMeC6H4 (1c), p-NO2C6H4 (1d), 1-naphthyl (1e), 2-furyl (1f), and 2-thienyl (1g)) undergo propargylallylation with allylic chlorides 2a−e (allyl chloride (2a), methallyl chloride (2b), 4-chloropent-2-ene (2c), cinnamyl chloride (2d)

  描述了一种通过膦-钯催化的活化烯烃，烯丙基氯化物和烯丙基锡烷的三组分组装法合成1,7-烯炔衍生物的有效方法。取代的芳基亚乙基丙二腈1a - g（RCH C（CN）2：R = C 6 H 5（1a），p -ClC 6 H 4（1b），p -OMeC 6 H 4（1c），p -NO 2 C 6 H 4（1d），1-萘基（1e），2-呋喃基（1f）和2-噻吩基（1 g））与烯丙基氯化物2a - e（烯丙基氯化物（2a），甲烯丙基氯化物（2b），4-氯戊-2-烯（2c）进行炔丙基化，肉桂基氯（2D），和3- chlorocyclohexene（2E））和ñ -tributylallenylstannane（ñ -Bu 3 SNCH ç CH 2，图3a）中的Pd（PPh的存在3）4在甲苯中，得到相应的1,7- -烯炔衍生物4a− m好至极好的产量。催化反应具有高度的区域选择性，其中炔丙基基团加到碳