5-benzoyl-6-(bromomethyl)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione | 443667-38-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 5-benzoyl-6-(bromomethyl)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione
• 英文别名: 5-benzoyl-6-(bromomethyl)-1,3-dimethylpyrimidine-2,4(1H,3H)dione；5-benzoyl-6-(bromomethyl)-1,3-dimethyl-1H-pyrimidine-2,4-dione；5-benzoyl-6-bromomethyl-1,3-dimethylpyrimidine-2,4-dione；5-benzoyl-6-bromomethyl-1,3-dimethyluracil；5-benzoyl-6-(bromomethyl)-1,3-dimethylpyrimidine-2,4-dione
• CAS: 443667-38-7
• 化学式: C₁₄H₁₃BrN₂O₃
• 分子量: 337.173
• InChiKey: BARUKSFSFFTJBU-UHFFFAOYSA-N

物化性质

• 熔点：
  169-171 °C(Solv: isopropanol (67-63-0))
• 沸点：
  413.2±55.0 °C(Predicted)
• 密度：
  1.518±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  57.7
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-benzoyl-6-(bromomethyl)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione 在 三氟乙酸 作用下， 以 乙醇 、 1,2-二氯乙烷 为溶剂， 反应 1.25h， 生成 7,9-dimethyl-11-phenyl-6-(5-hydroxymethylfuran-2-yl)-5,6-dihydropyrimido[4',5':3,4]pyrrolo[1,2-a]quinoxaline-8,10(7H,9H)-dione
  参考文献：
  名称：

  Potent, Metabolically Stable Benzopyrimido-pyrrolo-oxazine-dione (BPO) CFTR Inhibitors for Polycystic Kidney Disease

  摘要：

  We previously reported the discovery of pyrimido-pyrrolo-quinoxalinedione (PPQ) inhibitors of the cystic fibrosis transmentbrane conductance regulator (CFTR) chlordoide channel and showed their efficacy in an organ culture model of polycystic kidney disease (PKD) (J. Med. Chem. 2009, 52, 6447-6455). Here, we report related benzopyrimido-pyrrolo-oxazinedione (BPO) CFTR inhibitors. To establish structure activity relationships and select lead compound(s) with improved potency, metabolic stability, and aqueous solubility compared to the most potent prior compound 8 (PPQ:102, IC50 similar to 90 nM), we synthesized 16 PPQanalogues and 11 BPO analogues. The analogues were efficiently synthesized in 5-6 steps and 11-61% overall yield. Modification of 8 by bromine substitution at the 5-position of the furan ring, replacement of the secondary amine with an ether bridge, and carboxylation, gave 6-(5-bromofuran-2-yl)-7,9-dimethyl-8,10-dioxo-11-phenyl-7,8,9,10-tetrahydro-6H-benzo[b]pyrimido (4',5':3,4]pyrrolo [1,2-d] [1,4]oxazine-2-carboxylic acid 42 (BPO-27), which fully inhibited CFTR with IC50 similar to 8 nM and, compared to 8, had >10-fold greater metabolic stability and much greater polarity/aqueous solubility. In an embryonic kidney culture model of PKD, 42 prevented cyst growth with IC50 similar to 100 nM. Benzopyrimido-pyrrolo-oxazinediones such as 42 are potential development candidates for antisecretory therapy of PKD.

  DOI：

  10.1021/jm200505e
• 作为产物：
  描述：

  1,3,4-三甲基尿嘧啶 在 N-溴代丁二酰亚胺(NBS) 、 偶氮二异丁腈 、 zinc(II) oxide 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成 5-benzoyl-6-(bromomethyl)-1,3-dimethylpyrimidine-2,4(1H,3H)-dione
  参考文献：
  名称：

  骨架形形色色的创新[2,1- c ] -1,4-奥氮平和[1,4]-喹喔啉体系的合成

  摘要：

  建立了一种高效，创新的[2,1- c ] -1、4-氧杂氮杂和[1,4]-喹喔啉杂环以及具体的嘧啶基-吡咯基基序的合成方法。最初，通过微波辐射通过乙酰溴甲基嘧啶二酮和邻氨基苯甲醇或邻苯二胺甲基苯甲酸酯之间的分子内碱催化的环化作用来安装吡咯环。此外，通过非常规的Pictet-Spengler反应策略，通过酸催化与多种醛的缩合反应构建了奥沙平和喹喔啉骨架。这项工作的重要方面是建立具有潜在医学价值的新型杂环系统。

  DOI：

  10.1021/acscombsci.5b00093

文献信息

• TRICYCLIC COMPOUNDS
  申请人：AHMED Mahbub

  公开号：US20140171412A1

  公开（公告）日：2014-06-19

  The present invention provides a compound of formula I or a pharmaceutically acceptable salt thereof; 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化合物或其药用可接受的盐；以及其治疗用途。本发明还提供了一种药理活性剂的组合和药物组合物。
• Palladium-catalyzed synthesis of pyrimido[5’,4’:3,4]pyrrolo[1,2-f]phenanthridine-12,14(11H,13H)-diones and related compounds
  作者：M. A. Shevchenko、Y. N. Tkachenko、A. V. Astakhov、O. V. Khazipov、R. V. Tyurin、D. V. Pasyukov、V. A. Tafeenko、O. A. Kravchenko、V. M. Chernyshev

  DOI：10.1007/s11172-018-2277-2

  日期：2018.9

  Representatives of the new heterocyclic system, pyrimido[5’,4’:3,4]pyrrolo[1,2-f]phenanthridine, were obtained via the intramolecular C–H-arylation of 6-aryl-5-(2-bromophenyl) pyrrolo[3,4-d]pyrimidine-2,4-diones catalyzed by palladium complexes with N-heterocyclic carbene ligands (Pd/NHC).

  新杂环系统的代表嘧啶[5',4':3,4]吡咯并[1,2-f]菲啶是通过6-芳基-5-(2-溴苯基)的分子内C-H-芳基化获得的。 ) 吡咯并 [3,4-d] 嘧啶-2,4-二酮由钯配合物与 N-杂环卡宾配体 (Pd/NHC) 催化。
• A concise synthesis of 2-(2-aminothiophene)-benzimidazoles by one-pot multicomponent reaction
  作者：Li-Hsun Chen、Ying-Sheng Chuang、Bharat D. Narhe、Chung-Ming Sun

  DOI：10.1039/c3ra41545g

  日期：——

  A one-pot synthesis of 2-aminothiophene linked benzimidazoles was achieved by utilizing 2-cyanomethyl benzimidazoles in a modified Gewald multicomponent reaction. The synthetic strategy of the reaction involved treatment of 2-(cyanomethyl)-benzimdazole with aldehydes containing an active methylene group and sulfur powder under refluxing conditions. The multicomponent reaction proceeded via Knoevenagel condensation of 2-(cyanomethyl)-benzimdazole with aldehyde to generate an α,β-unsaturated nitrile followed by cyclization with molecular sulfur under basic conditions to give biologically relevant 2-(2-aminothiophene)-benzimidazoles in good yields.

  通过在改进的 Gewald 多组分反应中利用 2-氰甲基苯并咪唑，实现了 2-氨基噻吩连接的苯并咪唑的一锅法合成。该反应的合成策略是在回流条件下用含有活性亚甲基的醛和硫粉处理2-(氰甲基)-苯并咪唑。该多组分反应通过 2-(氰甲基)-苯并咪唑与醛的 Knoevenagel 缩合进行，生成 α,β-不饱和腈，然后在碱性条件下与分子硫环化，得到生物相关的 2-(2-氨基噻吩)-苯并咪唑。产量。
• PYRIMIDO-PYRROLO-QUINOXALINEDIONE INHIBITORS OF CYSTIC FIBROSIS TRANSMEMBRANE CONDUCTANCE REGULATOR PROTEIN AND USES THEREFOR
  申请人：Verkman Alan S.

  公开号：US20120208822A1

  公开（公告）日：2012-08-16

  Provided herein are pyrimido-pyrrolo-quinoxalinedione (PPQ) compounds, and compositions comprising these compounds, that inhibit cystic fibrosis transmembrane conductance regulator (CFTR) mediated ion transport and that are useful for treating diseases and disorders associated with aberrantly increased CFTR chloride channel activity. The compounds, and compositions comprising the compounds, described herein are useful for treating diseases, disorders, and sequelae of diseases, disorders, and conditions that are associated with aberrantly increased CFTR activity, for example, polycystic kidney disease. The compounds may be used for inhibiting expansion or preventing formation of cysts in persons who have polycystic kidney disease.

  本文提供了嘧啶并吡咯并喹啉二酮（PPQ）化合物和包含这些化合物的组合物，它们抑制囊性纤维化跨膜传导调节因子（CFTR）介导的离子传输，并且可用于治疗与异常增加的CFTR氯离子通道活性相关的疾病和疾病。本文所述的化合物和包含这些化合物的组合物可用于治疗与异常增加的CFTR活性相关的疾病、疾病和病情后遗症，例如多囊肾病。这些化合物可用于抑制多囊肾病患者的囊肿扩张或预防囊肿的形成。
• Pyrimido-pyrrolo-oxazine-dione compound inhibitors of the cystic fibrosis transmembrane conductance regulator protein and uses therefor
  申请人：Verkman Alan S.

  公开号：US09062073B2

  公开（公告）日：2015-06-23

  Provided herein are benzopyrimido-pyrrolo-oxazine-dione (BPO) compounds and pyrimido-pyrrolo-quinoxalinedione (PPQ) compounds, and compositions comprising these compounds, that inhibit cystic fibrosis transmembrane conductance regulator (CFTR) mediated ion transport and that are useful for treating diseases and disorders associated with aberrantly increased CFTR chloride channel activity, such as polycystic kidney disease and secretory diarrheas. The compounds and compositions comprising the compounds described herein may be used for inhibiting expansion or preventing formation of cysts in persons who have polycystic kidney disease.

  本文提供了苯并嘧啶基吡咯并噁嗪二酮（BPO）化合物和嘧啶基吡咯并喹啉二酮（PPQ）化合物，以及包含这些化合物的组合物，它们能够抑制囊性纤维化跨膜传导调节器（CFTR）介导的离子传输，并且适用于治疗与异常增加的CFTR氯通道活性相关的疾病和障碍，例如多囊肾病和分泌性腹泻。所述的化合物和组合物可以用于抑制多囊肾病患者的囊肿扩张或预防囊肿的形成。