6-amino-1-(4-chlorobenzyl)-uracil | 179486-47-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 英文名称: 6-amino-1-(4-chlorobenzyl)-uracil
• 英文别名: 6-Amino-1-[(4-chlorophenyl)methyl]-1,2,3,4-tetrahydropyrimidine-2,4-dione；6-amino-1-[(4-chlorophenyl)methyl]pyrimidine-2,4-dione
• CAS: 179486-47-6
• 化学式: C₁₁H₁₀ClN₃O₂
• mdl: MFCD06260079
• 分子量: 251.672
• InChiKey: HGWQNUBKCNLWAI-UHFFFAOYSA-N

物化性质

• 密度：
  1.432±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  75.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6-amino-1-(4-chlorobenzyl)-uracil 在 sodium nitrite 作用下， 以 溶剂黄146 为溶剂， 生成 6-amino-1-(4-chlorobenzyl)-5-nitroso-uracil
  参考文献：
  名称：

  Aryl thioxanthines

  摘要：

  本发明涉及公式（I）的新化合物： ##STR1## 其中Q3R3和Q8R8如本文所述。这些化合物具有PDE-IV抑制活性和相对于PDE-III抑制的改进选择性。本发明还揭示了使用所述化合物的制药组合物和治疗方法。

  公开号：

  US06066641A1
• 作为产物：
  描述：

  N-(4-氯苄基)脲 在 sodium hydroxide 作用下， 以 乙醇-D1 、 水 、 乙酸酐 为溶剂， 反应 1.0h， 生成 6-amino-1-(4-chlorobenzyl)-uracil
  参考文献：
  名称：

  Exploring Selective Inhibition of the First Bromodomain of the Human Bromodomain and Extra-terminal Domain (BET) Proteins

  摘要：

  A midthroughput screening follow-up program targeting the first bromodomain of the human BRD4 protein, BRD4(BD1), identified an acetylated-mimic xanthine derivative inhibitor. This compound binds with an affinity in the low micromolar range yet exerts suitable unexpected selectivity in vitro against the other members of the bromodomain and extra-terminal domain (BET) family. A structure-based program pinpointed a role of the ZA loop, paving the way for the development of potent and selective BET-BRDi probes.

  DOI：

  10.1021/acs.jmedchem.5b01708

文献信息

• Aryl thioxanthines
  申请人：Euro-Celtique S.A.

  公开号：US06066641A1

  公开（公告）日：2000-05-23

  The present invention relates to novel compounds of the formula (I): ##STR1## wherein Q.sub.3 R.sub.3 and Q.sub.8 R.sub.8 are described herein. The compounds possess PDE-IV inhibitory activity and improved selectivity with regard to PDE-III inhibition. Also disclosed are pharmaceutical compositions and methods of treatment utilizing the disclosed compounds.

  本发明涉及公式（I）的新化合物： ##STR1## 其中Q3R3和Q8R8如本文所述。这些化合物具有PDE-IV抑制活性和相对于PDE-III抑制的改进选择性。本发明还揭示了使用所述化合物的制药组合物和治疗方法。
• One-Pot Synthesis and Molecular Modeling Studies of New Bioactive Spiro-Oxindoles Based on Uracil Derivatives as SARS-CoV-2 Inhibitors Targeting RNA Polymerase and Spike Glycoprotein
  作者：Samar A. El-Kalyoubi、Ahmed Ragab、Ola A. Abu Ali、Yousry A. Ammar、Mohamed G. Seadawy、Aya Ahmed、Eman A. Fayed

  DOI：10.3390/ph15030376

  日期：——

  The first outbreak in Wuhan, China, in December 2019 was reported about severe acute coronaviral syndrome 2 (SARS-CoV-2). The global coronavirus disease 2019 (COVID-19) pandemic in 2020 resulted in an extremely high potential for dissemination. No drugs are validated in large-scale studies for significant effectiveness in the clinical treatment of COVID-19 patients, despite the worsening trends of COVID-19. This study aims to design a simple and efficient cyclo-condensation reaction of 6-aminouracil derivatives 2a–e and isatin derivatives 1a–c to synthesize spiro-oxindoles 3a–d, 4a–e, and 5a–e. All compounds were tested in vitro against the SARS-CoV-2. Four spiro[indoline-3,5′-pyrido[2,3-d:6,5-d’]dipyrimidine derivatives 3a, 4b, 4d, and 4e showed high activities against the SARS-CoV-2 in plaque reduction assay and were subjected to further RNA-dependent-RNA-polymerase (RdRp) and spike glycoprotein inhibition assay investigations. The four compounds exhibited potent inhibitory activity ranging from 40.23 ± 0.09 to 44.90 ± 0.08 nM and 40.27 ± 0.17 to 44.83 ± 0.16 nM, respectively, when compared with chloroquine as a reference standard, which showed 45 ± 0.02 and 45 ± 0.06 nM against RdRp and spike glycoprotein, respectively. The computational study involving the docking studies of the binding mode inside two proteins ((RdRp) (PDB: 6m71), and (SGp) (PDB: 6VXX)) and geometrical optimization used to generate some molecular parameters were performed for the most active hybrids.

  2019年12月，中国武汉爆发了严重急性呼吸综合征冠状病毒2（SARS-CoV-2）。2020年，全球新冠肺炎（COVID-19）大流行导致了极高的传播潜力。尽管COVID-19的趋势不断恶化，但目前没有任何药物在大规模研究中被证明对COVID-19患者的临床治疗具有显著的有效性。本研究旨在设计一种简单高效的6-氨基尿嘧啶衍生物2a-e和吲哚酮衍生物1a-c的环缩合反应，以合成螺环氧吲哚3a-d，4a-e和5a-e。所有化合物均在体外对SARS-CoV-2进行了测试。四个螺[吲哚-3,5'-吡啶[2,3-d:6,5-d']]二嘧啶衍生物3a、4b、4d和4e在减少斑点实验中表现出高活性，并进一步进行了RNA依赖性RNA聚合酶（RdRp）和尖刺糖蛋白抑制试验的研究。与氯喹作为参考标准相比，这四种化合物在抑制RdRp和尖刺糖蛋白方面表现出强大的抑制活性，分别为40.23±0.09至44.90±0.08 nM和40.27±0.17至44.83±0.16 nM。计算研究涉及到两种蛋白内的结合模式的对接研究（RdRp（PDB：6m71）和SGp（PDB：6VXX）），并进行了一些分子参数的几何优化，以生成最活跃的杂交物。
• Aryl isoguanines
  申请人：Euro-Celtique, S.A.

  公开号：US06440979B1

  公开（公告）日：2002-08-27

  Disclosed are compounds having formula (II): wherein: Q3, Q6a, Q6b and Q8 are independently a bond, C1-8 alkylene, C2-8 alkenylene and C2-8 alkynylene, and R3, R6a, R6b and R8 are independently hydrogen, aryl or heteroraryl, optionally substituted by halogen, hydroxy, alkoxy, nitro, cyano and carboxy, provided that: Q3R3 is not hydrogen or methyl. The compounds are effective PDE IV inhibitors and possess improved PDE IV inhibition and improved selectivity with regard to PDE III inhibition.

  本发明涉及具有以下式子（II）的化合物：其中：Q3，Q6a，Q6b和Q8独立地是键，C1-8烷基，C2-8烯基和C2-8炔基，而R3，R6a，R6b和R8独立地是氢，芳基或杂芳基，可选择地被卤素，羟基，烷氧基，硝基，氰基和羧基取代，条件是：Q3R3不是氢或甲基。这些化合物是有效的PDE IV抑制剂，并具有改进的PDE IV抑制和改进的选择性，与PDE III抑制有关。
• EP0814809A4
  申请人：——

  公开号：EP0814809A4

  公开（公告）日：1998-04-01
• ARYL THIOXANTHINES
  申请人：Euroceltique S.A.

  公开号：EP0814809A1

  公开（公告）日：1998-01-07