N-[4-[6-tert-butyl-5-methoxy-8-(6-methoxy-2-oxo-1H-pyridin-3-yl)-3-quinolyl]phenyl]methanesulfonamide | 1257830-82-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: N-[4-[6-tert-butyl-5-methoxy-8-(6-methoxy-2-oxo-1H-pyridin-3-yl)-3-quinolyl]phenyl]methanesulfonamide
• 英文别名: N-{4-[6-tert-butyl-5-methoxy-8-(6-methoxy-2-oxo-1,2-dihydro-pyridin-3-yl)-quinolin-3-yl]-phenyl}-methanesulfonamide；N-[4-[6-tert-butyl-5-methoxy-8-(6-methoxy-2-oxo-1H-pyridin-3-yl)quinolin-3-yl]phenyl]methanesulfonamide
• CAS: 1257830-82-2
• 化学式: C₂₇H₂₉N₃O₅S
• 分子量: 507.61
• InChiKey: KGISHOZEUVOVTB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  36
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  N-[4-(8-bromo-6-tert-butyl-5-methoxy-3-quinolyl)phenyl]methanesulfonamide 在 四(三苯基膦)钯 、 氢溴酸 、 sodium carbonate 、 溶剂黄146 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 生成 N-[4-[6-tert-butyl-5-methoxy-8-(6-methoxy-2-oxo-1H-pyridin-3-yl)-3-quinolyl]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：de Vicente Fidalgo Javier

  公开号：US20100311760A1

  公开（公告）日：2010-12-09

  Compounds having the formula I wherein wherein R 1 , R 2 , R 3 , R 4 , X 1 , X 2 , X 3 and X 4 and 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.

  具有化学式I的化合物，其中R1、R2、R3、R4、X1、X2、X3和X4如本文所定义，是丙型肝炎病毒NS5b聚合酶抑制剂。还公开了治疗HCV感染和抑制HCV复制的组合物和方法。
• PHARMACEUTICAL COMPOSITION WITH IMPROVED BIOAVAILABILITY, SAFETY AND TOLERABILITY
  申请人：Hoffmann-LaRoche Inc.

  公开号：US20140128431A1

  公开（公告）日：2014-05-08

  The invention relates to solid dispersions of poorly soluble compounds formed by coprecipitation, resulting in improved bioavailability, safety and tolerability. The invention also relates to Purified Eudragit L100-55 used to prepare such solid dispersions.
• US8026253B2
  申请人：——

  公开号：US8026253B2

  公开（公告）日：2011-09-27
• US8487103B2
  申请人：——

  公开号：US8487103B2

  公开（公告）日：2013-07-16
• [EN] HETEROCYCLIC ANTIVIRAL COMPOUNDS<br/>[FR] COMPOSÉS ANTIVIRAUX HÉTÉROCYCLIQUES
  申请人：HOFFMANN LA ROCHE

  公开号：WO2010142656A1

  公开（公告）日：2010-12-16

  Compounds having the formula (I) wherein wherein R1, R2, R3, R4, X1, X2, X3 and X4 and 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.