8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile | 846038-96-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile
• 英文别名: 8-oxoacenaphthyleno[2,1-b]pyrrole-9-carbonitrile
• CAS: 846038-96-8
• 化学式: C₁₅H₆N₂O
• 分子量: 230.225
• InChiKey: VQYSTSIAUDPRJH-UHFFFAOYSA-N

物化性质

• 熔点：
  276-278 °C(Solv: acetonitrile (75-05-8))
• 沸点：
  441.8±55.0 °C(Predicted)
• 密度：
  1.44±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  53.2
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile 在 硫酸 、 potassium carbonate 作用下， 以 乙腈 为溶剂， 反应 10.0h， 生成 8-Oxo-8H-acenaphtho[1,2-b]pyrrole-9-carboxylic acid benzyl ester
  参考文献：
  名称：

  具有氨基链取代的新型novel [1,2-b]吡咯-羧酸酯的设计，合成和抗肿瘤评价。

  摘要：

  制备了8-氧代-8H-ac并[1,2-b]吡咯-9-羧酸酯和衍生物，并评估了其对A549和P388细胞系的细胞毒性。基于新型发色团前体8-oxo-8H-ac [1,2-b]吡咯-9-腈1，将极不溶的1转化为可溶的酯5，并从5获得了一系列3-氨基衍生物通过5种胺与各种胺的温和S（N）Ar（H）反应 生物学评估表明，在母体酯5a-5f中，甲酯5a具有最高的细胞毒性，IC（50）值为0.45和0.80 microM（分别针对A549和P388），而5f的3-氨基衍生物4b和4c具有在3-氨基衍生物中，溴显示出最高的活性（IC（50）值为0.019-0.60 microM）。

  DOI：

  10.1016/j.bmc.2006.02.016
• 作为产物：
  描述：

  苊醌 在 potassium carbonate 作用下， 以 二氯甲烷 、 乙腈 为溶剂， 生成 8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile
  参考文献：
  名称：

  新型含硒苊并[1,2-b]吡咯衍生物：合成与生物活性

  摘要：

  图形摘要 摘要 设计并合成了七种新型含硒苊并 [1,2-b] 吡咯衍生物，并通过 MTT 四唑鎓染料测定评估了它们的细胞毒性作用。两种化合物表现出良好的抗癌活性。

  DOI：

  10.1080/10426507.2015.1072187

文献信息

• ACENAPHTHO HETEROCYCLIC COMPOUND AND APPLICATION THEREOF
  申请人：Zhang Zhichao

  公开号：US20130123492A1

  公开（公告）日：2013-05-16

  The present invention relates to acenaphtho heterocyclic compounds and their uses in manufacturing the BH3 mimetics as Bcl-2-like protein inhibitors. Structures are shown in the following: Statistical analysis of their bio-activities showed these compounds exhibit better BH3 mimicking property than the reported compounds. These compounds can simulate BH3-only protein, competitively bind and antagonizing Bcl-2 and Mcl-1 proteins in vitro and in cells, and then induce apoptosis. Therefore, they all can be used in the manufactures of anticancer compounds.

  本发明涉及蒽醌杂环化合物及其在制造类似Bcl-2蛋白抑制剂的BH3模拟物中的用途。结构如下所示：对它们的生物活性进行的统计分析表明，这些化合物表现出比已报告的化合物更好的BH3模拟性能。这些化合物可以模拟BH3-只蛋白，在体外和细胞中与Bcl-2和Mcl-1蛋白竞争性结合和拮抗，然后诱导细胞凋亡。因此，它们都可以用于抗癌化合物的制造。
• 3-Thiomorpholin-8-oxo-8<i>H</i>-acenaphtho[1,2-<i>b</i>]pyrrole-9-carbonitrile (S1) Based Molecules as Potent, Dual Inhibitors of B-Cell Lymphoma 2 (Bcl-2) and Myeloid Cell Leukemia Sequence 1 (Mcl-1): Structure-Based Design and Structure−Activity Relationship Studies
  作者：Zhichao Zhang、Guiye Wu、Feibo Xie、Ting Song、Xilong Chang

  DOI：10.1021/jm101181u

  日期：2011.2.24

  discovery of a dual inhibitor of Bcl-2 and Mcl-1, 3-thiomorpholin-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (3, S1). Here we report a structure-guided design in combination with structure−activity relationship studies to exploit the difference in the p2 binding pocket of Bcl-2 and Mcl-1, from which a novel dual inhibitor 3-(4-aminophenylthio)-8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile (6h) was

  我们最近描述了Bcl-2和Mcl-1的双重抑制剂3- thiomorpholin -8-oxo-8 H -ac [1,2 - b ]吡咯-9-腈（3，S1）的发现。在这里，我们报告结构指导的设计与结构活性关系研究相结合，以利用Bcl-2和Mcl-1在p2结合口袋中的差异，从而从中获得新型的双重抑制剂3-（4-氨基苯硫基）-8-获得了oxo-8 H -ac [1,2 - b ]吡咯-9-腈（6h），显示出对Mcl-1（5 nM）的IC 50值显着提高，Mcl-1 / Bak破坏潜力更大，并且因此，细胞毒性比3增加了10倍。
• Acenaphtho[1,2-<i>b</i>]pyrrole-Based Selective Fibroblast Growth Factor Receptors 1 (FGFR1) Inhibitors: Design, Synthesis, and Biological Activity
  作者：Zhuo Chen、Xin Wang、Weiping Zhu、Xianwen Cao、Linjiang Tong、Honglin Li、Hua Xie、Yufang Xu、Shaoying Tan、Dong Kuang、Jian Ding、Xuhong Qian

  DOI：10.1021/jm200258t

  日期：2011.6.9

  series of acenaphtho[1,2-b]pyrrole derivatives as potent and selective inhibitors of fibroblast growth factor receptor 1 (FGFR1) were designed and synthesized. In silico target prediction revealed that tyrosine kinases might be the potential targets of the representative compound 2, which was subsequently validated by enzyme-linked immunosorbent assay (ELISA) for its selective and active FGFR1 inhibition

  设计并合成了一系列新颖的of [1,2- b ]吡咯衍生物，作为成纤维细胞生长因子受体1（FGFR1）的有效抑制剂和选择性抑制剂。在计算机靶标中预测，酪氨酸激酶可能是代表性化合物2的潜在靶标，随后通过酶联免疫吸附测定（ELISA）验证了其对多种酪氨酸激酶的选择性和活性FGFR1抑制作用。结构-活性关系（SAR）分析通过分子对接模拟在ATP结合位点辅助证明苊并[1,2- b ]吡咯羧酸酯（2 - 5）是具有IC FGFR1的有效抑制剂50值范围从19到77 nM。此外，这些化合物对表达FGFR的癌细胞系表现出有利的生长抑制特性，其IC 50值范围从微摩尔到亚微摩尔。Western印迹分析表明，化合物2，3，和图2b FGFR1的活化抑制和细胞外信号调节激酶1/2（ERK1 / 2）。
• Ratiometric and reusable fluorescent nanoparticles for Zn2+ and H2PO4− detection in aqueous solution and living cells
  作者：Chunsheng He、Weiping Zhu、Yufang Xu、Ye Zhong、Juan Zhou、Xuhong Qian

  DOI：10.1039/c0jm01925a

  日期：——

  In this work, three kinds of core–shell silica nanoparticle-based fluorescent materials were prepared based on a modified Stöber–Van Blaaderen method. They were characterized by transmission electron microscopy (TEM), scanning electron microscopy (SEM), dynamic light scattering (DLS), FT-IR, and several other spectroscopic methods. Firstly, The silica@sensor-1 nanoparticle (SSN) showed high selectivity toward Zn2+, which can detect Zn2+ in aqueous solution and living cells. It also can be reused to detect Zn2+ for at least four cycles after a simple regeneration. Secondly, to create a ratiometric measurement platform, the dye-2@silica nanoparticles (DSN), a new class of core–shell fluorescent silica nanoparticles were prepared with an acenaphtho[1, 2-b]pyrrol-9-carbonitrile chromophore derivative as the inner reference. It showed negligible sensing properties towards Zn2+, and the fluorescent intensity was not subjected to interference induced by pH change. Thirdly, the dye-2@silica@sensor-1 nanoparticles (DSSN), with the above reference dye buried inside the silica matrix and a layer of chemosensors anchored onto the surface of silica nanoparticles were prepared. DSSN showed not only the same sensing ability as SSN, but also a clear ratiometric fluorescent signal toward Zn2+ in aqueous solutions and living cells. On the other hand, H2PO4− is a well-known Zn2+ binder, so the [DSSN@Zn2+] complex was found to ratiometrically detect H2PO4−. It responded to H2PO4− at a neutral aqueous solution with a detection limit lower than 6 × 10−6 M. Moreover, the ratio of fluorescence intensity was linearly increased in the range 6∼500 μM of H2PO4−, which implies a potential application for the quantitation of H2PO4− in aqueous solution. To the best of our knowledge, this is the first example of core–shell silica nanoparticle-based fluorescent materials that can be repeatedly used to ratiometrically detect Zn2+ and H2PO4− in 100% neutral aqueous solutions.

  在这项工作中，基于改进的Stöber–Van Blaaderen方法制备了三种基于核壳二氧化硅纳米粒子的荧光材料。通过透射电子显微镜（TEM）、扫描电子显微镜（SEM）、动态光散射（DLS）、傅里叶变换红外光谱（FT-IR）及其他几种光谱方法对其进行了表征。首先，二氧化硅@sensor-1纳米粒子（SSN）对Zn2+表现出高选择性，能够在水溶液和活细胞中检测Zn2+。经过简单的再生后，它还可以重复使用至少四个循环以检测Zn2+。其次，为了创建一个比率测量平台，制备了染料-2@二氧化硅纳米粒子（DSN），这是一种新的核壳荧光二氧化硅纳米粒子，内部使用了acenaphtho[1, 2-b]pyrrol-9-carbonitrile染料衍生物作为参考。它对Zn2+几乎没有感应特性，荧光强度不受pH变化引起的干扰。第三，制备了染料-2@二氧化硅@sensor-1纳米粒子（DSSN），其中上述参考染料埋在二氧化硅基质中，并在二氧化硅纳米粒子表面锚定了一层化学传感器。DSSN不仅具有与SSN相同的检测能力，而且在水溶液和活细胞中对Zn2+表现出明显的比率荧光信号。另一方面，H2PO4⁻是众所周知的Zn2+结合剂，因此发现[DSSN@Zn2+]复合物能够以比率方式检测H2PO4⁻。它在中性水溶液中对H2PO4⁻的检测限低于6 × 10⁻⁶ M。此外，荧光强度的比率在6～500 μM范围内呈线性增加，暗示在水溶液中定量H2PO4⁻的潜在应用。据我们所知，这是首次展示可以重复使用的基于核壳二氧化硅纳米粒子的荧光材料，能够在100%中性水溶液中以比率方式检测Zn2+和H2PO4⁻。
• ACENAPHTHO HETEROCYCLE COMPOUNDS, CYCLODEXTRIN INCLUSION COMPOUNDS AND COMPLEXES, AND USES IN THE MANUFACTURES OF BH3 PROTEIN ANALOGUE, BCL-2 FAMILY PROTEIN INHIBITORS THEREOF
  申请人：Zhang Zhichao

  公开号：US20110251188A1

  公开（公告）日：2011-10-13

  The present invention relates to acenaphtho heterocyclic compounds, cyclodextrin inclusion compounds and complexes thereof, and their uses in manufacturing the inhibitors of BH3 analogue, Bcl-2 family proteins. The acenaphtho heterocyclic compounds are obtained by introducing oxo-, thio-, carbonyl, ester or acyl in the 3-, 4- and 6-position of 8-oxo-8H-acenaphtho[1,2-b]pyrrole-9-carbonitrile, or further substituting 9-cyano with carboxyl, ester or amide. The compounds can simulate BH3-only protein, competitively binding and antagonizing Bcl-2, Bel-X L and Mcl-1 proteins in vitro or intracellular, to induce cell apoptosis. The cyclodextrin inclusion compounds and complexes can improve the effects. Therefore, they all can be used in the manufactures of anticancer compounds.

  本发明涉及乙酰基环戊异维生素类化合物、环糊精包合物及其复合物，以及它们在制造BH3类似物、Bcl-2家族蛋白抑制剂中的应用。乙酰基环戊异维生素类化合物是通过在8-氧代-8H-乙酰基环戊[1,2-b]吡咯-9-碳腈的3、4和6位引入氧、硫、羰基、酯或酰基，或进一步用羧基、酯或酰胺取代9-氰基而得到的。这些化合物可以模拟BH3-only蛋白，在体外或细胞内与Bcl-2、Bel-XL和Mcl-1蛋白竞争性结合和拮抗，诱导细胞凋亡。环糊精包合物和复合物可以提高效果。因此，它们都可以用于抗癌化合物的制造。