5-羟基-4-氧代-2-噻吩-2-基-1H-嘧啶-6-甲酰胺 | 849475-71-4

• 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-羟基-4-氧代-2-噻吩-2-基-1H-嘧啶-6-甲酰胺
• 英文名称: 5,6-Dihydroxy-2-thiophen-2-yl-pyrimidine-4-carboxylic acid amide
• 英文别名: 5,6-Dihydroxy-2-(2-thienyl)pyrimidine-4-carboxamide；5-hydroxy-6-oxo-2-thiophen-2-yl-1H-pyrimidine-4-carboxamide
• CAS: 849475-71-4
• 化学式: C₉H₇N₃O₃S
• 分子量: 237.239
• InChiKey: SCXAUENZKSNKQP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  16
• 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：
  133
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  5-羟基-4-氧代-2-噻吩-2-基-1H-嘧啶-6-甲酰胺 在 三氟乙酸酐 作用下， 以 二氯甲烷 、 氯仿 为溶剂， 以71%的产率得到5,6-Dihydroxy-2-thiophen-2-yl-pyrimidine-4-carbonitrile
  参考文献：
  名称：

  Active site inhibitors of HCV NS5B polymerase. The development and pharmacophore of 2-thienyl-5,6-dihydroxypyrimidine-4-carboxylic acid

  摘要：

  5,6-Dihydroxypyrimidine-4-carboxylic acids are a promising series of hepatitis C virus (HCV) NS5B polymerase inhibitors that bind at the active site of the enzyme. Here we report a simple 2-thienyl substituted analogue that shows 10-fold improved activity over the original lead, and which allowed us to further delineate the key elements of the pharmacophore of this class of inhibitor. This work led to the identification of a trifluoromethyl acylsulfonamide group as a viable replacement for the C4 carboxylic acid in this series. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2004.07.075
• 作为产物：
  描述：

  5,6-二羟基-2-噻吩-2-基-嘧啶-4-羧酸甲酯 在 氨 作用下， 以 甲醇 为溶剂， 反应 72.0h， 以45%的产率得到5-羟基-4-氧代-2-噻吩-2-基-1H-嘧啶-6-甲酰胺
  参考文献：
  名称：

  Dihydroxypyrimidine-4-carboxamides作为新型有效和选择性的HIV整合酶抑制剂。

  摘要：

  人类免疫缺陷病毒1型（HIV-1）整合酶是复制所需的三种组成型病毒酶之一，是化学疗法干预AIDS的合理靶标，最近在临床环境中也得到了证实。我们在这里报告的N-苄基5,6-二羟基嘧啶-4-羧酰胺的设计和合成作为一类药物，对HIV整合酶催化的链转移过程具有有效的抑制作用。在当前的研究中，对这些分子进行了结构修饰，以检查其对HIV整合酶抑制效能的影响。该系列中最有趣的化合物之一是2- [1-（二甲基氨基）-1-甲基乙基] -N-（4-氟苄基）-5,6-二羟基嘧啶-4-羧酰胺38，CIC95为78 nM。在血清蛋白存在下进行基于细胞的测定。

  DOI：

  10.1021/jm070027u

文献信息

• [EN] DIHYDROXYPYRIMIDINE CARBOXAMIDE INHIBITORS OF HIV INTEGRASE<br/>[FR] INHIBITEURS DE L'INTEGRASE DU VIH A BASE DE DIHYDROXYPYRIMIDINE CARBOXAMIDE
  申请人：ANGELETTI P IST RICHERCHE BIO

  公开号：WO2003035076A1

  公开（公告）日：2003-05-01

  4,5-Dihydroxypyrimidine-6-carboxamides of formula (I); are described as inhibitors of HIV integrase and inhibitors of HIV replication, wherein R?1, R2, R3 and R4¿ are defined herein. These compounds are useful in the prevention and treatment of infection by HIV and in the prevention, delay in the onset, and treatment of AIDS. The compounds are employed against HIV infection and AIDS as compounds per se or in the form of pharmaceutically acceptable salts. The compounds and their salts can be employed as ingredients in pharmaceutical compositions, optionally in combination with other antivirals, immunomodulators, antibiotics or vaccines. Methods of preventing, treating or delaying the onset of AIDS and methods of preventing or treating infection by HIV are also described.

  公式为（I）的4,5-二羟基嘧啶-6-羧酰胺被描述为HIV整合酶抑制剂和HIV复制抑制剂，其中R?1，R2，R3和R4¿在此定义。这些化合物对于预防和治疗HIV感染以及预防、延迟发病和治疗艾滋病非常有用。这些化合物作为化合物本身或药物可接受的盐的形式用于对抗HIV感染和艾滋病。这些化合物及其盐可作为药物组合中的成分，可选地与其他抗病毒药物、免疫调节剂、抗生素或疫苗组合使用。还描述了预防、治疗或延迟艾滋病发病的方法以及预防或治疗HIV感染的方法。
• DIHYDROXYPYRIMIDINE CARBOXAMIDE INHIBITORS OF HIV INTEGRASE
  申请人：Istituto di Richerche di Biologia Molecolare P. Angeletti S.p.A.

  公开号：EP1441734A1

  公开（公告）日：2004-08-04
• Dihydroxypyrimidine-4-carboxamides as Novel Potent and Selective HIV Integrase Inhibitors
  作者：Paola Pace、M. Emilia Di Francesco、Cristina Gardelli、Steven Harper、Ester Muraglia、Emanuela Nizi、Federica Orvieto、Alessia Petrocchi、Marco Poma、Michael Rowley、Rita Scarpelli、Ralph Laufer、Odalys Gonzalez Paz、Edith Monteagudo、Fabio Bonelli、Daria Hazuda、Kara A. Stillmock、Vincenzo Summa

  DOI：10.1021/jm070027u

  日期：2007.5.1

  chemotherapeutic intervention in the treatment of AIDS that has also recently been confirmed in the clinical setting. We report here on the design and synthesis of N-benzyl-5,6-dihydroxypyrimidine-4-carboxamides as a class of agents which exhibits potent inhibition of the HIV-integrase-catalyzed strand transfer process. In the current study, structural modifications on these molecules were made in order

  人类免疫缺陷病毒1型（HIV-1）整合酶是复制所需的三种组成型病毒酶之一，是化学疗法干预AIDS的合理靶标，最近在临床环境中也得到了证实。我们在这里报告的N-苄基5,6-二羟基嘧啶-4-羧酰胺的设计和合成作为一类药物，对HIV整合酶催化的链转移过程具有有效的抑制作用。在当前的研究中，对这些分子进行了结构修饰，以检查其对HIV整合酶抑制效能的影响。该系列中最有趣的化合物之一是2- [1-（二甲基氨基）-1-甲基乙基] -N-（4-氟苄基）-5,6-二羟基嘧啶-4-羧酰胺38，CIC95为78 nM。在血清蛋白存在下进行基于细胞的测定。
• Active site inhibitors of HCV NS5B polymerase. The development and pharmacophore of 2-thienyl-5,6-dihydroxypyrimidine-4-carboxylic acid
  作者：Ian Stansfield、Salvatore Avolio、Stefania Colarusso、Nadia Gennari、Frank Narjes、Barbara Pacini、Simona Ponzi、Steven Harper

  DOI：10.1016/j.bmcl.2004.07.075

  日期：2004.10

  5,6-Dihydroxypyrimidine-4-carboxylic acids are a promising series of hepatitis C virus (HCV) NS5B polymerase inhibitors that bind at the active site of the enzyme. Here we report a simple 2-thienyl substituted analogue that shows 10-fold improved activity over the original lead, and which allowed us to further delineate the key elements of the pharmacophore of this class of inhibitor. This work led to the identification of a trifluoromethyl acylsulfonamide group as a viable replacement for the C4 carboxylic acid in this series. (C) 2004 Elsevier Ltd. All rights reserved.