5,6-dihydroxy-2-(thiophen-2-yl)pyrimidine-4-carboxylic acid | 391680-79-8

• 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: 5,6-dihydroxy-2-(thiophen-2-yl)pyrimidine-4-carboxylic acid
• 英文别名: 2-(2-Thienyl)-4,5-dihydroxypyrimidine-6-carboxylate；5,6-Dihydroxy-2-thiophen-2-yl-pyrimidine-4-carboxylic acid；5-hydroxy-6-oxo-2-thiophen-2-yl-1H-pyrimidine-4-carboxylic acid
• CAS: 391680-79-8
• 化学式: C₉H₆N₂O₄S
• 分子量: 238.224
• InChiKey: SSOGKSFNCMYOPA-UHFFFAOYSA-N

物化性质

• 沸点：
  408.1±55.0 °C(Predicted)
• 密度：
  1.78±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 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：
  127
• 氢给体数：
  3
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  5,6-dihydroxy-2-(thiophen-2-yl)pyrimidine-4-carboxylic acid 在 盐酸 、 三乙胺 作用下， 生成 Phosphoric acid 4-(diethoxy-phosphoryloxy)-2-thiophen-2-yl-pyrimidin-5-yl ester diethyl ester
  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 盐酸 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 生成 5,6-dihydroxy-2-(thiophen-2-yl)pyrimidine-4-carboxylic acid
  参考文献：
  名称：

  HIV-1逆转录酶抑制剂的药理学要求，该抑制剂可在聚合催化周期中选择性地“冻结”预转移的复合物

  摘要：

  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。

  DOI：

  10.1016/j.bmc.2018.02.017

文献信息

• 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。
• Dihydroxypyrimidine carboxylic acids as viral polymerase inhibitors
  申请人：——

  公开号：US20040106627A1

  公开（公告）日：2004-06-03

  A class of 2-aryl-4,5-dihydroxy-6-carboxypyrimidines of formula (I): wherein Ar is an optionally substituted aryl or heterocyclic group; as well as compounds of formula (I) which are derivatised at one or more of the 4-hydroxy, 5-hydroxy or 6-carboxy groups; and tautomers thereof, and pharmaceutically acceptable salts or esters thereof; and inhibitors of viral polymerases, especially the hepatitis C virus (HCV) polymerase enzyme. 1

  2-芳基-4,5-二羟基-6-羧基嘧啶的一类化合物的化学式(I)：其中Ar是一个可选择地取代的芳基或杂环基；以及在4-羟基、5-羟基或6-羧基中的一个或多个位置衍生的化合物的化学式(I)；以及它们的互变异构体，以及它们的药用盐或酯；以及病毒聚合酶抑制剂，特别是乙型肝炎病毒（HCV）聚合酶酶。
• 2-(2-Thienyl)-5,6-dihydroxy-4-carboxypyrimidines as Inhibitors of the Hepatitis C Virus NS5B Polymerase:  Discovery, SAR, Modeling, and Mutagenesis
  作者：Uwe Koch、Barbara Attenni、Savina Malancona、Stefania Colarusso、Immacolata Conte、Marcello Di Filippo、Steven Harper、Barbara Pacini、Claudia Giomini、Steven Thomas、Ilario Incitti、Licia Tomei、Raffaele De Francesco、Sergio Altamura、Victor G. Matassa、Frank Narjes

  DOI：10.1021/jm051064t

  日期：2006.3.1

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

  公开号：EP1309566A1

  公开（公告）日：2003-05-14
• Anti-infective pyrimidines and uses thereof
  申请人：AbbVie Bahamas Ltd.

  公开号：EP2639226B1

  公开（公告）日：2016-08-31