methyl 5,6-dihydroxy-2-(3-nitro-2-thienyl)pyrimidine-4-carboxylate | 391680-96-9

• 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: methyl 5,6-dihydroxy-2-(3-nitro-2-thienyl)pyrimidine-4-carboxylate
• 英文别名: methyl 5-hydroxy-2-(3-nitrothiophen-2-yl)-6-oxo-1H-pyrimidine-4-carboxylate
• CAS: 391680-96-9
• 化学式: C₁₀H₇N₃O₆S
• 分子量: 297.248
• InChiKey: RPMMKHGABVFVPH-UHFFFAOYSA-N

物化性质

• 沸点：
  498.9±55.0 °C(Predicted)
• 密度：
  1.81±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  20
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  162
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  methyl 5,6-dihydroxy-2-(3-nitro-2-thienyl)pyrimidine-4-carboxylate 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 0.25h， 以43%的产率得到5,6-Dihydroxy-2-(3-nitro-thiophen-2-yl)-pyrimidine-4-carboxylic acid
  参考文献：
  名称：

  2-(2-Thienyl)-5,6-dihydroxy-4-carboxypyrimidines as Inhibitors of the Hepatitis C Virus NS5B Polymerase:  Discovery, SAR, Modeling, and Mutagenesis

  摘要：

  Infections caused by hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. The polymerase of HCV is responsible for the replication of viral RNA. We recently disclosed dihydroxypyrimidine carboxylates 2 as novel, reversible inhibitors of the HCV NS5B polymerase. This series was further developed into 5,6-dihydroxy-2-(2-thienyl)pyrimidine-4-carboxylic acids such as 34 (EC50 9.3 mu M), which now show activity in the cell-based HCV replication assay. The structure-activity relationship of these inhibitors is discussed in the context of their physicochemical properties and of the polymerase crystal structure. We also report the results of mutagenesis experiments which support the proposed binding model, which involves pyrophosphate-like chelation of the active site Mg ions.

  DOI：

  10.1021/jm051064t
• 作为产物：
  描述：

  dimethyl 2-({[1-amino(3-nitro-2-thienyl)methylene]amino}oxy)but-2-enedioate 以 xylene 为溶剂， 以48%的产率得到methyl 5,6-dihydroxy-2-(3-nitro-2-thienyl)pyrimidine-4-carboxylate
  参考文献：
  名称：

  2-(2-Thienyl)-5,6-dihydroxy-4-carboxypyrimidines as Inhibitors of the Hepatitis C Virus NS5B Polymerase:  Discovery, SAR, Modeling, and Mutagenesis

  摘要：

  Infections caused by hepatitis C virus (HCV) are a significant world health problem for which novel therapies are in urgent demand. The polymerase of HCV is responsible for the replication of viral RNA. We recently disclosed dihydroxypyrimidine carboxylates 2 as novel, reversible inhibitors of the HCV NS5B polymerase. This series was further developed into 5,6-dihydroxy-2-(2-thienyl)pyrimidine-4-carboxylic acids such as 34 (EC50 9.3 mu M), which now show activity in the cell-based HCV replication assay. The structure-activity relationship of these inhibitors is discussed in the context of their physicochemical properties and of the polymerase crystal structure. We also report the results of mutagenesis experiments which support the proposed binding model, which involves pyrophosphate-like chelation of the active site Mg ions.

  DOI：

  10.1021/jm051064t

文献信息

• DIHYDROXYPYRIMIDINE CARBOXYLIC ACIDS AS VIRAL POLYMERASE INHIBITORS
  申请人：ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A.

  公开号：EP1309566B1

  公开（公告）日：2009-10-07
• PYRIMIDINONE VIRAL POLYMERASE INHIBITORS
  申请人：ISTITUTO DI RICERCHE DI BIOLOGIA MOLECOLARE P. ANGELETTI S.P.A.

  公开号：EP1470113A1

  公开（公告）日：2004-10-27
• [EN] PYRIMIDINONE VIRAL POLYMERASE INHIBITORS<br/>[FR] INHIBITEURS PYRIMIDONE DE POLYMERASES VIRALES
  申请人：ANGELETTI P IST RICHERCHE BIO

  公开号：WO2003062211A1

  公开（公告）日：2003-07-31

  A class of pyrimidinone derivatives of formula (I): wherein Z, R1, R2 and R3 are as defined herein; and pharmaceutically acceptable salts thereof; are inhibitors of viral polymerases, especially the hepatitis C virus (HCV) polymerase enzyme.