5,6-二羟基-2-苯基嘧啶-4-羧酸 | 62222-38-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪类
• 中文名称: 5,6-二羟基-2-苯基嘧啶-4-羧酸
• 英文名称: 5,6-dihydroxy-2-phenylpyrimidine-4-carboxylic acid
• 英文别名: 5-hydroxy-6-oxo-2-phenyl-1,6-dihydro-pyrimidine-4-carboxylic acid；5,6-Dihydroxy-2-phenylpyrimidine-4-carboxylic acid；5-hydroxy-6-oxo-2-phenyl-1H-pyrimidine-4-carboxylic acid
• CAS: 62222-38-2
• 化学式: C₁₁H₈N₂O₄
• 分子量: 232.196
• InChiKey: ZCILTNACHNCSCB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  17
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  99
• 氢给体数：
  3
• 氢受体数：
  4

安全信息

• 海关编码：
  2933599090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335

反应信息

• 作为反应物：
  描述：

  5,6-二羟基-2-苯基嘧啶-4-羧酸 、 盐酸 生成 2-Phenyl-4,5-dihydroxy-pyrimidin
  参考文献：
  名称：

  CULBERTSON T. P., J. HETEROCYCL. CHEM., 1979, 16, NO 7, 1423-1424

  摘要：

  DOI：
• 作为产物：
  描述：

  苯甲酰胺肟 在 水 、 lithium hydroxide 作用下， 以 1,4-二氧六环 、 甲醇 、 邻二甲苯 为溶剂， 反应 12.67h， 生成 5,6-二羟基-2-苯基嘧啶-4-羧酸
  参考文献：
  名称：

  4,5-二羟基嘧啶甲基羧酸盐、羧酸和甲酰胺作为人巨细胞病毒 pUL89 核酸内切酶的抑制剂

  摘要：

  人巨细胞病毒 (HCMV) 末端酶复合物在 pUL89 (pUL89-C) 的 C 末端包含金属依赖性核酸内切酶。我们在此报告了二羟基嘧啶 (DHP) 酸 ( 14 )、甲酯 ( 13 ) 和酰胺 ( 15 ) 亚型作为 HCMV pUL89-C 抑制剂的设计、合成和表征。所有合成的类似物都在核酸内切酶测定和热位移测定 (TSA) 中进行测试，并进行分子对接以预测结合亲和力。尽管从所有三种亚型中鉴定出在亚 μM 范围内抑制 pUL89-C 的类似物，但酸 ( 14 ) 显示出比酯 ( 13 ) 和酰胺 ( 15 ) 更好的整体效力、显着更大的热位移和更好的对接分数). 在基于细胞的抗病毒试验中，六种类似物以中等活性抑制 HCMV (EC 50 = 14.4–22.8 μM)。酸亚型 ( 14 ) 表现出良好的体外ADME 特性，但渗透性较差。总体而言，我们的数据支持 DHP 酸亚型 ( 14

  DOI：

  10.1021/acs.jmedchem.2c00203

文献信息

• Preparation of 5-hydroxy-6-oxo-1,6-dihydropyrimidine compounds
  申请人：Dreher D. Spencer

  公开号：US20050090668A1

  公开（公告）日：2005-04-28

  5-Hydroxy-6-oxo-1,6-dihydropyrimidine compounds are prepared by the condensation of dihydroxyfumarate derivatives with amidines. The pyrimidine compounds are useful as intermediates in the preparation of pharmacologically active compounds.

  5-羟基-6-氧代-1,6-二氢嘧啶化合物是通过二羟基富马酸酯与胺基甲酸酯的缩合制备的。这些嘧啶化合物在制备药理活性化合物中作为中间体是有用的。
• Pharmacophore requirements for HIV-1 reverse transcriptase inhibitors that selectively “Freeze” the pre-translocated complex during the polymerization catalytic cycle
  作者：Cyrus M. Lacbay、Michael Menni、Jean A. Bernatchez、Matthias Götte、Youla S. Tsantrizos

  DOI：10.1016/j.bmc.2018.02.017

  日期：2018.5

  Reverse transcriptase (RT) is responsible for replicating the HIV-1 genome and is a validated therapeutic target for the treatment of HIV infections. During each cycle of the RT-catalyzed DNA polymerization process, inorganic pyrophosphate is released as the by-product of nucleotide incorporation. Small molecules were identified that act as bioisosteres of pyrophosphate and can selectively freeze the

  逆转录酶（RT）负责复制HIV-1基因组，并且是经验证的治疗HIV感染的治疗靶标。在RT催化的DNA聚合过程的每个循环中，无机焦磷酸盐作为核苷酸掺入的副产物释放。鉴定出的小分子充当焦磷酸盐的生物等排体，并且可以在DNA或RNA模板引物酶复合物的预易位阶段选择性冻结HIV-1 RT的催化循环。
• Highly selective synthesis of 2-substituted-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxylic acid derivatives using a novel protected dihydroxyfumarate
  作者：Spencer D. Dreher、Norihiro Ikemoto、Venita Gresham、Jinchu Liu、Peter G. Dormer、Jaume Balsells、David Mathre、Thomas J. Novak、Joseph D. Armstrong

  DOI：10.1016/j.tetlet.2004.06.028

  日期：2004.7

  A high yielding (50-96%) route to 2-substituted-5-hydroxy-6-oxo-1,6-dihydropyrimidine-4-carboxylic acid derivatives has been developed using a rationally designed dihydroxyfumarate derivative. The fully unprotected pyrimidinone heterocycle was prepared in quantitative yield upon treatment with HCl. (C) 2004 Elsevier Ltd. All rights reserved.
• RNase H Active Site Inhibitors of Human Immunodeficiency Virus Type 1 Reverse Transcriptase: Design, Biochemical Activity, and Structural Information
  作者：Thorsten A. Kirschberg、Mini Balakrishnan、Neil H. Squires、Tiffany Barnes、Katherine M. Brendza、Xiaowu Chen、Eugene J. Eisenberg、Weili Jin、Nilima Kutty、Stephanie Leavitt、Albert Liclican、Qi Liu、Xiaohong Liu、John Mak、Jason K. Perry、Michael Wang、William J. Watkins、Eric B. Lansdon

  DOI：10.1021/jm900597q

  日期：2009.10.8

  Pyrimidinol carboxylic acids were designed as inhibitors of HIV-1 RNase H function. These molecules can coordinate to two divalent metal ions in the RNase H active site. Inhibition of enzymatic activity was measured in a biochemical assay, but no antiviral effect was observed. Binding wits demonstrated via a solid state structure of the isolated p15-Ec domain of HIV-1 RT showing inhibitor and two Mn(II) ions bound to the RNase H active site.
• HCV NS5b RNA-Dependent RNA Polymerase Inhibitors:  From α,γ-Diketoacids to 4,5-Dihydroxypyrimidine- or 3-Methyl-5- hydroxypyrimidinonecarboxylic Acids. Design and Synthesis
  作者：Vincenzo Summa、Alessia Petrocchi、Victor G. Matassa、Marina Taliani、Ralph Laufer、Raffaele De Francesco、Sergio Altamura、Paola Pace

  DOI：10.1021/jm0494669

  日期：2004.10.1

  A new class of the HCV NS5b RNA-dependent RNA polymerase inhibitors, the dihyroxypyrimidinecarboxylic acid derivative, was designed from a diketoacid and meconic acid derivative discovered by screening. Mechanism of action and essential moieties required for activity were identified. The corresponding N-methylpyrimidinone was also prepared; both classes are novel, reversible, and selective inhibitors of the HCV NS5b polymerase with improved druglike characteristics.