dibutyl 1H-imidazole-4,5-dicarboxylate | 59399-27-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: dibutyl 1H-imidazole-4,5-dicarboxylate
• 英文别名: dibutyl imidazole-4,5-dicarboxylate；butyl 4,5-imidazoledicarboxylate；1H-imidazole-4,5-dicarboxylic acid dibutyl ester；Imidazol-4,5-dicarbonsaeure-dibutylester
• CAS: 59399-27-8
• 化学式: C₁₃H₂₀N₂O₄
• 分子量: 268.313
• InChiKey: VGGTVIRRIHHUEK-UHFFFAOYSA-N

物化性质

• 熔点：
  107.5-108.5 °C(Solv: water (7732-18-5); methanol (67-56-1))
• 沸点：
  405.7±25.0 °C(Predicted)
• 密度：
  1.137±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  81.3
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  dibutyl 1H-imidazole-4,5-dicarboxylate 在 甲醇 、 sodium methylate 、 sodium hydride 、 溶剂黄146 作用下， 以 乙腈 为溶剂， 反应 27.0h， 生成 6-(Dodecylamino)-3,7-dihydroimidazo[4,5-e][1,3]diazepine-4,8-dione
  参考文献：
  名称：

  Potent Inhibition of NTPase/Helicase of the West Nile Virus by Ring-Expanded (“Fat”) Nucleoside Analogues

  摘要：

  A series of ring-expanded ("fat") nucleoside analogues (RENs) containing the 6-aminoimidazo-[4,5-e] [1,3]diazepine-4,8-dione ring system have been synthesized and screened for inhibition of NTPase/helicase of the West Nile Virus (WNV). To assess the selectivity of RENs against the viral enzymes, a truncated form of human enzyme Suv3((Delta1-159)) was also included in the study. Ring-expanded nucleosides 16, 17, and 19, which possess the long C-12, C-14, and C-18 side-chains, respectively, at position 6, as well as the ring-expanded heterocycle 39, which contains aralkyl substitution at position 1, were all found to have excellent profiles of activity and selectivity toward the viral versus human enzymes against the West Nile Virus (IC50 ranging 1-10 muM). Compound 30, while being an equally potent inhibitor of WNV, was found to be somewhat less selective, whereas compound 36, which is an alpha-anomeric counterpart of 30, exhibited potent and selective inhibition of WN-V (IC50 1-3 muM). The same compounds that showed potent inhibition of viral helicase activity completely failed to show any activity against the viral NTPase reaction even up to 500 muM. However, at concentrations >500 muM of RENs and the ATP concentrations >10 times the K-m value of the enzyme, a significant activation of NTPase activity was observed. This activating effect underwent further dramatic enhancement (>1000%) by further increases in ATP concentration in the reaction mixture, suggesting that the viral helicase and NTPase reactions are not coupled. A tentative mechanistic model has been proposed to explain the observed results.

  DOI：

  10.1021/jm030277k
• 作为产物：
  描述：

  咪唑-4,5-二羧酸 、 正丁醇 在 硫酸 作用下， 反应 22.0h， 以45.5 g的产率得到dibutyl 1H-imidazole-4,5-dicarboxylate
  参考文献：
  名称：

  Caldwell, A. Gordon; Harris, C. John; Stepney, Ray, Journal of the Chemical Society. Perkin transactions I, 1980, p. 495 - 505

  摘要：

  DOI：

文献信息

• [EN] IMIDAZOPYRROLIDINONE DERIVATIVES AND THEIR USE IN THE TREATMENT OF DISEASE<br/>[FR] DÉRIVÉS IMIDAZOPYRROLIDINONE ET LEUR UTILISATION DANS LE TRAITEMENT DE MALADIES
  申请人：NOVARTIS AG

  公开号：WO2014191894A1

  公开（公告）日：2014-12-04

  The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了化合物(I)或其药学上可接受的盐；制造本发明化合物的方法及其治疗用途。本发明还提供了药理活性剂的组合和药物组合物。
• Synthesis and in vitro anti-hepatitis B and C virus activities of ring-expanded (‘fat’) nucleobase analogues containing the imidazo[4,5-e][1,3]diazepine-4,8-dione ring system
  作者：Peng Zhang、Ning Zhang、Brent E. Korba、Ramachandra S. Hosmane

  DOI：10.1016/j.bmcl.2005.09.015

  日期：2005.12

  part of our structure-activity relationship studies, we report here the synthesis and in vitro anti-HBV and anti-HCV activities of a number of ring-expanded ('fat') nucleobases containing the imidazo[4,5-e][1,3]diazepine-4,8-dione ring system. One of the compounds, ZP-88, exhibited a good activity/toxicity profile against HBV by inhibition of the synthesis of extracellular virion release (EC(50)=1.7microM

  作为我们的结构-活性关系研究的一部分，我们在这里报告许多含有咪唑[4,5-e] [ 1,3]二氮杂-4,8-​​二酮环系统。其中一种化合物ZP-88通过抑制细胞外病毒体释放的合成（EC（50）= 1.7microM，CC（50）= 286microM，SI = 168）和细胞内HBV表现出良好的针对HBV的活性/毒性复制的中间体（EC（50）= 8.4microM，CC（50）= 286microM，SI = 34）在培养的人类肝母细胞瘤2.2.15细胞中。相比之下，大多数抗HCV的化合物仅具有边缘活性/毒性特征，尽管仍比参考化合物利巴韦林更好。
• Dual inhibition of HCV and HIV by ring-expanded nucleosides containing the 5:7-fused imidazo[4,5- e ][1,3]diazepine ring system. In vitro results and implications
  作者：Ning Zhang、Peng Zhang、Andrea Baier、Lucyna Cova、Ramachandra S. Hosmane

  DOI：10.1016/j.bmcl.2013.12.121

  日期：2014.2

  Examples of ring-expanded nucleosides (RENs), represented by general structures 1 and 2, exhibited dual anti-HCV and anti-HIV activities in both cell culture systems and the respective target enzyme assays, including HCV NTPase/helicase and human RNA helicase DDX3. Since HCV is a leading co-infection in late stage HIV AIDS patients, often leading to liver cirrhosis and death, the observed dual inhibition

  由一般结构1和2表示的扩环核苷 (REN) 的例子在细胞培养系统和各自的靶酶测定中表现出双重抗 HCV 和抗 HIV 活性，包括 HCV NTPase/解旋酶和人 RNA 解旋酶 DDX3 . 由于 HCV 是晚期 HIV AIDS 患者的主要合并感染，通常会导致肝硬化和死亡，因此观察到的靶核苷类似物对 HCV 和 HIV 的双重抑制对治疗感染了 HCV 的 HIV 患者具有潜在的有益意义。
• IMIDAZOPYRROLIDINE DERIVATIVES AND THEIR USE IN THE TREATMENT OF DISEASE
  申请人：BLANK Jutta

  公开号：US20160108047A1

  公开（公告）日：2016-04-21

  The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了公式（I）的化合物或其药学上可接受的盐；本发明还提供了制造本发明化合物的方法及其治疗用途。本发明还提供了一种药理活性剂的组合和制药组合物。
• IMIDAZOPYRROLIDINONE DERIVATIVES AND THEIR USE IN THE TREATMENT OF DISEASE
  申请人：Novartis AG

  公开号：EP3412675A1

  公开（公告）日：2018-12-12

  The present invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof; a method for manufacturing the compounds of the invention, and its therapeutic uses. The present invention further provides a combination of pharmacologically active agents and a pharmaceutical composition.

  本发明提供了一种式（I）化合物或其药学上可接受的盐； 一种制造本发明化合物的方法及其治疗用途。本发明进一步提供了一种药理活性剂的组合物和一种药物组合物。