N-[4-[2-tert-butyl-4-(2,4-dioxopyrimidin-1-yl)quinazolin-7-yl]phenyl]methanesulfonamide | 1354455-81-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: N-[4-[2-tert-butyl-4-(2,4-dioxopyrimidin-1-yl)quinazolin-7-yl]phenyl]methanesulfonamide
• 英文别名: N-{4-[2-tert-butyl-4-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)quinazolin-7-yl]phenyl}methanesulfonamide
• CAS: 1354455-81-4
• 化学式: C₂₃H₂₃N₅O₄S
• 分子量: 465.533
• InChiKey: VQDSLPHXKJTIEC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  33
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  130
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  2-氨基-4-溴苯甲酰胺 在 四(三苯基膦)钯 、 sodium carbonate 、 caesium carbonate 、 三乙胺 、 N,N-二异丙基乙胺 、 三氯氧磷 作用下， 以 甲醇 、 二氯甲烷 、 二甲基亚砜 、 甲苯 、 苯 为溶剂， 反应 11.0h， 生成 N-[4-[2-tert-butyl-4-(2,4-dioxopyrimidin-1-yl)quinazolin-7-yl]phenyl]methanesulfonamide
  参考文献：
  名称：

  Discovery of N-[4-[6-tert-Butyl-5-methoxy-8-(6-methoxy-2-oxo-1H-pyridin-3-yl)-3-quinolyl]phenyl]methanesulfonamide (RG7109), a Potent Inhibitor of the Hepatitis C Virus NS5B Polymerase

  摘要：

  In the past few years, there have been many advances in the efforts to cure patients with hepatitis C virus (HCV). The ultimate goal of these efforts is to develop a combination therapy consisting of only direct-antiviral agents (DAAs). In this paper, we discuss our efforts that led to the identification of a bicyclic template with potent activity against the NS5B polymerase, a critical enzyme on the life cycle of HCV. In continuation of our exploration to improve the stilbene series, the 3,5,6,8-tetrasubstituted quinoline core was identified as replacement of the stilbene moiety. 6-Methoxy-2(1H)-pyridone was identified among several heterocyclic headgroups to have the best potency. Solubility of the template was improved by replacing a planar aryl linker with a saturated pyrrolidine. Profiling of the most promising compounds led to the identification of quinoline 41 (RG7109), which was selected for advancement to clinical development.

  DOI：

  10.1021/jm401329s

文献信息

• HETEROCYCLIC ANTIVIRAL COMPOUNDS
  申请人：Schoenfeld Ryan Craig

  公开号：US20120009144A1

  公开（公告）日：2012-01-12

  Compounds having the formula I wherein R 1 , R 2 , R 3 and X are as defined herein are Hepatitis C virus NS5b polymerase inhibitors. Also disclosed are compositions and methods for treating an HCV infection and inhibiting HCV replication.

  具有公式I的化合物，其中R1、R2、R3和X的定义如本文所述，是丙型肝炎病毒NS5b聚合酶抑制剂。还公开了用于治疗HCV感染和抑制HCV复制的组合物和方法。
• US8329712B2
  申请人：——

  公开号：US8329712B2

  公开（公告）日：2012-12-11
• [EN] HETEROCYCLIC ANTIVIRAL COMPOUNDS<br/>[FR] COMPOSÉS ANTIVIRAUX HÉTÉROCYCLIQUES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2012004212A1

  公开（公告）日：2012-01-12

  Compounds having the formula I wherein R1, R2, R3 and X are as defined herein are Hepatitis C virus NS5b polymerase inhibitors. Also disclosed are compositions and methods for treating an HCV infection and inhibiting HCV replication.