4H,9H-diimidazo<1,5-a; 1',5'-d>pyrazine-5,10-dione-1,6-dicarboxylic dichloride | 59157-06-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 咪唑并[1,5-a]吡嗪
• 英文名称: 4H,9H-diimidazo<1,5-a; 1',5'-d>pyrazine-5,10-dione-1,6-dicarboxylic dichloride
• 英文别名: 5,10-dioxo-5,10-dihydrodiimidazo[1,5-a:1',5'-d]pyrazine-1,6-dicarbonyl dichloride；5,10-dioxo-5H,10H-diimidazo[1,5-a:1',5'-d]pyrazine-1,6-dicarbonyl dichloride；5;10-dioxo-5H;10H-diimidazo[1;5-a:1';5'-d]pyrazine-1;6-dicarbonyl dichloride；5,10-dioxo-5H,10H-diimidazo[1,5-a;1',5'-d]pyrazinedicarbonyl-1,6-dichloride；5,10-dioxo-5,10-dihydroimidazol[1,5-a:1',5'-d]pyrazine-1,6-diacid chloride；5,10-dioxo-5H,10H-diimidazo[1,5-a;1',5'-d]pyrazine-1,6-dicarbonyl dichloride；5,10-Dioxo-5H,10H-diimidazo(1,5-a:1',5'-d)pyrazine-1,6-dicarbonyl dichloride；2,8-dioxo-1,5,7,11-tetrazatricyclo[7.3.0.03,7]dodeca-3,5,9,11-tetraene-4,10-dicarbonyl chloride
• CAS: 59157-06-1
• 化学式: C₁₀H₂Cl₂N₄O₄
• 分子量: 313.056
• InChiKey: DSXPZEAWGCENHU-UHFFFAOYSA-N

物化性质

• 熔点：
  >200 °C (decomp)
• 沸点：
  729.7±70.0 °C(Predicted)
• 密度：
  2.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  104
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  4H,9H-diimidazo<1,5-a; 1',5'-d>pyrazine-5,10-dione-1,6-dicarboxylic dichloride 在 三氯化铝 、 三乙胺 作用下， 以 氯仿 、 硝基苯 为溶剂， 反应 3.0h， 生成 N-(2-aminophenyl)-4-benzoyl-1H-imidazole-5-carboxamide
  参考文献：
  名称：

  摘要：

  DOI：

  10.1023/a:1023784811891
• 作为产物：
  描述：

  咪唑-4,5-二羧酸 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 甲苯 为溶剂， 生成 4H,9H-diimidazo<1,5-a; 1',5'-d>pyrazine-5,10-dione-1,6-dicarboxylic dichloride
  参考文献：
  名称：

  脂肪酸合酶硫酯酶结构域的抑制剂，具有针对乳腺癌细胞的改善的细胞毒性和血浆中的稳定性。

  摘要：

  众所周知，许多癌症沉迷于不断供应的脂肪酸（FAs），并且显示出从头开始的FA合成。关键的脂肪形成酶，脂肪酸合酶（FASN）的上调是人类癌症及其前体病变的近乎普遍的特征，并且与化学抗性，肿瘤转移和患者生存期降低有关。已经显示出FASN抑制在杀死癌细胞方面是有效的，但是该领域的进展由于脱靶效应和候选化合物的不良药物性能而受到阻碍。Sanford-Burnham化学基因组学中心使用纯化的FASN硫酯酶（FASN-TE）域从高通量筛选工作中鉴定出了我们的首批产品（化合物1）。尽管是纯化的FASN-TE的有效抑制剂，化合物1在小鼠血浆中证明高度不稳定，并且在体外对乳腺癌（BC）细胞仅具有微弱的细胞毒性。合成，细胞毒性测试和血浆稳定性评估的迭代过程用于鉴定新的前导物（化合物41）。与四氢-4-亚甲基-2S-辛基-5-氧代-3R呋喃甲酸（抑制FASN的文献标准）相比，该铅对多种BC细胞系的细胞毒性更大，

  DOI：

  10.1124/jpet.119.258947

文献信息

• [EN] AMIDO-SUBSTITUTED CYCLOHEXANE DERIVATIVES<br/>[FR] DÉRIVÉS DE CYCLOHEXANE À SUBSTITUTION AMIDO
  申请人：BAYER PHARMA AG

  公开号：WO2018078009A1

  公开（公告）日：2018-05-03

  The present invention relates to amido-substituted cyclohexane compounds of general formula (I) : in which m, A, R4, R6, R7, R8, R9, R10 and R11 are as defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neoplasms, as a sole agent or in combination with other active ingredients.

  本发明涉及一般式(I)的酰胺取代的环己烷化合物，其中m、A、R4、R6、R7、R8、R9、R10和R11如本文所定义，以及制备所述化合物的方法，用于制备所述化合物的有用中间体化合物，包含所述化合物的药物组合物和组合物，以及利用所述化合物制造用于治疗或预防疾病的药物组合物，特别是肿瘤，作为唯一药剂或与其他活性成分结合使用。
• [EN] AMIDO-SUBSTITUTED AZOLE COMPOUNDS<br/>[FR] COMPOSÉS AZOLE AMIDO-SUBSTITUÉS
  申请人：BAYER PHARMA AG

  公开号：WO2017055313A1

  公开（公告）日：2017-04-06

  The present invention relates to compounds of general formula (I), in which X1, X2, R1, R2, R4, R5, R7, and R8 are as defined herein, to methods of preparing said compounds, to intermediate compounds useful for preparing said compounds, to pharmaceutical compositions and combinations comprising said compounds and to the use of said compounds for manufacturing a pharmaceutical composition for the treatment or prophylaxis of a disease, in particular of neoplasms, as a sole agent or in combination with other active ingredients.

  本发明涉及一般式(I)的化合物，其中X1、X2、R1、R2、R4、R5、R7和R8如本文所定义，涉及制备所述化合物的方法，用于制备所述化合物的有用中间体化合物，包括所述化合物的药物组合物和组合物，以及利用所述化合物制造用于治疗或预防疾病的药物组合物，特别是肿瘤，作为唯一药剂或与其他活性成分组合使用。
• Parallel Synthesis of an Imidazole-4,5-dicarboxamide Library Bearing Amino Acid Esters and Alkanamines
  作者：Rosanna Solinas、John DiCesare、Paul Baures

  DOI：10.3390/molecules13123149

  日期：——

  The imidazole-4,5-dicarboxylic acid scaffold is readily derivatized with amino acid esters and alkanamines to afford compounds with intramolecularly hydrogen bonded conformations that mimic substituted purines and therefore are hypothesized to be potential inhibitors of kinases through competitive binding to the ATP site. In this work, a total of 126 dissymmetrically disubstituted imidazole-4,5-dicarboxamides with amino acid ester and alkanamide substituents were prepared by parallel synthesis. The library members were purified by column chromatography on silica gel and the purified compounds characterized by LC-MS with LC detection at 214 nm. A selection of the final compounds was also analyzed by 1H-NMR spectroscopy. The analytically pure final products have been submitted to the Molecular Library Small Molecule Repository (MLSMR) for screening in the Molecular Library Screening Center Network (MLSCN) as part of the NIH Roadmap.

  咪唑-4,5-二羧酸骨架易于与氨基酸酯和烷基胺进行衍生化，得到具有分子内氢键的构象类似取代嘌呤的化合物，因此被假设为通过竞争性结合ATP位点成为潜在的激酶抑制剂。在本研究中，通过平行合成法制备了总共126种不对称二取代的咪唑-4,5-二羧酰胺，其取代基为氨基酸酯和烷基酰胺。这些化合物库成员通过硅胶柱层析进行纯化，并采用LC-MS技术在214 nm波长下进行检测，以鉴定纯化后的化合物。部分最终产物还通过1H-NMR光谱进行了分析。这些分析纯的最终产物已提交至分子库小分子数据库（MLSMR），用于在分子库筛选中心网络（MLSCN）中进行筛选，作为NIH路线图计划的一部分。
• Parallel Synthesis of Peptide-Like Macrocycles Containing Imidazole-4,5-dicarboxylic Acid
  作者：Zhigang Xu、Kraig A. Wheeler、Paul W. Baures

  DOI：10.3390/molecules17055346

  日期：——

  We prepared a series of peptide-like 14-membered macrocycles containing an imidazole-4,5-dicarboxylic acid scaffold by using known coupling reagents and protecting group strategies. Yields of the purified macrocycles were poor on average, yet seemingly independent of amino acid substitution or stereochemistry. The macrocycles retain some level of conformational variability as observed by both molecular modeling and X-ray crystallography. These macrocycles represent a new class of structures for further development and for future application in high-throughput screening against a variety of biological targets.

  我们用已知的偶联试剂和保护基策略制备了一系列包含咪唑-4,5-二羧酸骨架的14源肽样大环。纯化后的大环平均产率较低，但似乎与氨基酸的取代或立体化学无关。这些大环保留了一定程度的构象变化水平，既通过分子建模也通过X射线晶体学观察到。这些大环代表了一类新的结构，可进一步开发并用于针对各种生物靶标的高通量筛选。
• Parallel Synthesis of a Library of Symmetrically- and Dissymmetrically-disubstituted Imidazole-4,5-dicarboxamides Bearing Amino Acid Esters
  作者：Rosanna Solinas、John DiCesare、Paul Baures

  DOI：10.3390/molecules14010352

  日期：——

  The imidazole-4,5-dicarboxylic acid scaffold is readily derivatized with amino acid esters to afford symmetrically- and dissymmetrically-disubstituted imidazole-4,5-dicarboxamides with intramolecularly hydrogen bonded conformations that predispose the presentation of amino acid pharmacophores. In this work, a total of 45 imidazole-4,5-dicarboxamides bearing amino acid esters were prepared by parallel synthesis. The library members were purified by column chromatography on silica gel and the purified compounds characterized by LC-MS with LC detection at 214 nm. A selection of the final compounds was also analyzed by 1H-NMR spectroscopy. The analytically pure final products have been submitted to the Molecular Library Small Molecule Repository (MLSMR) for screening in the Molecular Library Screening Center Network (MLSCN) as part of the NIH Roadmap.

  咪唑-4,5-二羧酸骨架可以通过氨基酸酯进行方便的衍生化，从而获得具有内分子氢键构象的对称和不对称二取代咪唑-4,5-二胺，这些构象有利于氨基酸药效团的呈现。在本研究中，通过平行合成制备了共计45种含氨基酸酯的咪唑-4,5-二胺。文库成员通过硅胶柱层析纯化，纯化后的化合物通过LC-MS进行表征，LC检测波长为214 nm。此外，部分最终化合物还通过1H-NMR光谱进行了分析。分析纯的最终产品已提交至分子库小分子库（MLSMR），用于作为NIH路线图的一部分，在分子库筛选中心网络（MLSCN）进行筛选。