2-[4-(2-Chlorophenylmethylaminocarbonylamino)thien-3-yl]-4,5-dihydroxypyrimidine-6-carboxylate | 391680-81-2

• 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: 2-[4-(2-Chlorophenylmethylaminocarbonylamino)thien-3-yl]-4,5-dihydroxypyrimidine-6-carboxylate
• 英文别名: 2-[4-[(2-Chlorophenyl)methylcarbamoylamino]-3-thienyl]-5,6-dihydroxy-pyrimidine-4-carboxylic acid；2-[4-[(2-chlorophenyl)methylcarbamoylamino]thiophen-3-yl]-5-hydroxy-6-oxo-1H-pyrimidine-4-carboxylic acid
• CAS: 391680-81-2
• 化学式: C₁₇H₁₃ClN₄O₅S
• 分子量: 420.833
• InChiKey: MOXUYQABLSKNFX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  168
• 氢给体数：
  5
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  在 lithium hydrochloride monohydrate 、 水 作用下， 以 四氢呋喃 为溶剂， 生成 2-[4-(2-Chlorophenylmethylaminocarbonylamino)thien-3-yl]-4,5-dihydroxypyrimidine-6-carboxylate
  参考文献：
  名称：

  2-(3-Thienyl)-5,6-dihydroxypyrimidine-4-carboxylic acids as inhibitors of HCV NS5B RdRp

  摘要：

  A series of 2-(3-thienyl)-5,6-dihydroxypyrimidine-4-carboxylic acid inhibitors of the hepatitis C virus (HCV) NS5B polymerase enzyme are reported. Sulfonyl urea substituted analogs in this series proved to be the most potent active site non-nucleoside inhibitors of NS5B reported to date. These compounds had low nanomolar enzyme inhibition across HCV genotypes 1-3 and showed single digit micromolar inhibition in the HCV replicon assay. This improved cell-based activity allowed the binding mode of these compounds to be probed by selection of resistant mutations against compound 21. The results generated are in broad agreement with the previously proposed binding model for this compound class. (C) 2009 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2009.06.106

文献信息

• 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。
• 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
• US7091209B2
  申请人：——

  公开号：US7091209B2

  公开（公告）日：2006-08-15
• 2-(3-Thienyl)-5,6-dihydroxypyrimidine-4-carboxylic acids as inhibitors of HCV NS5B RdRp
  作者：Barbara Pacini、Salvatore Avolio、Caterina Ercolani、Uwe Koch、Giovanni Migliaccio、Frank Narjes、Laura Pacini、Licia Tomei、Steven Harper

  DOI：10.1016/j.bmcl.2009.06.106

  日期：2009.11

  A series of 2-(3-thienyl)-5,6-dihydroxypyrimidine-4-carboxylic acid inhibitors of the hepatitis C virus (HCV) NS5B polymerase enzyme are reported. Sulfonyl urea substituted analogs in this series proved to be the most potent active site non-nucleoside inhibitors of NS5B reported to date. These compounds had low nanomolar enzyme inhibition across HCV genotypes 1-3 and showed single digit micromolar inhibition in the HCV replicon assay. This improved cell-based activity allowed the binding mode of these compounds to be probed by selection of resistant mutations against compound 21. The results generated are in broad agreement with the previously proposed binding model for this compound class. (C) 2009 Published by Elsevier Ltd.