N-[4-[7-tert-butyl-5-(2,4-dioxopyrimidin-1-yl)-8-methoxy-2-quinolyl]phenyl]methanesulfonamide | 1246277-51-9

• 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-[7-tert-butyl-5-(2,4-dioxopyrimidin-1-yl)-8-methoxy-2-quinolyl]phenyl]methanesulfonamide
• 英文别名: N-(4-(7-tert-butyl-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)-8-methoxyquinolin-2-yl)phenyl)methanesulfonamide.；N-{4-[7-tert-butyl-5-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-8-methoxyquinolin-2-yl]phenyl}methanesulfonamide；N-[4-[7-tert-butyl-5-(2,4-dioxopyrimidin-1-yl)-8-methoxyquinolin-2-yl]phenyl]methanesulfonamide
• CAS: 1246277-51-9
• 化学式: C₂₅H₂₆N₄O₅S
• 分子量: 494.571
• InChiKey: SNKSUTBCVIHXOR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  126
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  5-bromo-3-tert-butyl-2-methoxyaniline 在 铁粉 吡啶 、 potassium phosphate 、 copper(l) iodide 、 pyridine-2-carboxylic acid (2-cyanophenyl)amide 、 氯化铵 作用下， 以 甲醇 、 二氯甲烷 、 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 24.0h， 生成 N-[4-[7-tert-butyl-5-(2,4-dioxopyrimidin-1-yl)-8-methoxy-2-quinolyl]phenyl]methanesulfonamide
  参考文献：
  名称：

  [EN] HETEROCYCLIC ANTIVIRAL COMPOUNDS
  [FR] COMPOSÉS ANTIVIRAUX HÉTÉROCYCLIQUES

  摘要：

  具有化学式（I）的化合物，其中R1、R2、R3和X的定义如下，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。

  公开号：

  WO2012020037A1

文献信息

• [EN] ANTIVIRAL COMPOUNDS AND USES THEREOF<br/>[FR] COMPOSÉS ANTIVIRAUX ET LEURS UTILISATIONS
  申请人：ABBOTT LAB

  公开号：WO2010111437A1

  公开（公告）日：2010-09-30

  This invention relates to: (a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.

  这项发明涉及：(a) 抑制HCV等化合物及其盐；(b) 用于制备这种化合物和盐的中间体；(c) 包括这种化合物和盐的组合物；(d) 制备这种中间体、化合物、盐和组合物的方法；(e) 使用这种化合物、盐和组合物的方法；以及(f) 包括这种化合物、盐和组合物的试剂盒。
• Discovery of <i>N</i>-[4-[6-<i>tert</i>-Butyl-5-methoxy-8-(6-methoxy-2-oxo-1<i>H</i>-pyridin-3-yl)-3-quinolyl]phenyl]methanesulfonamide (RG7109), a Potent Inhibitor of the Hepatitis C Virus NS5B Polymerase
  作者：Francisco X. Talamas、Sarah C. Abbot、Shalini Anand、Ken A. Brameld、David S. Carter、Jun Chen、Dana Davis、Javier de Vicente、Amy D. Fung、Leyi Gong、Seth F. Harris、Petra Inbar、Sharada S. Labadie、Eun K. Lee、Remy Lemoine、Sophie Le Pogam、Vincent Leveque、Jim Li、Joel McIntosh、Isabel Nájera、Jaehyeon Park、Aruna Railkar、Sonal Rajyaguru、Michael Sangi、Ryan C. Schoenfeld、Leanna R. Staben、Yunchou Tan、Joshua P. Taygerly、Armando G. Villaseñor、Paul E. Weller

  DOI：10.1021/jm401329s

  日期：2014.3.13

  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.
• ANTIVIRAL COMPOUNDS AND USES THEREOF
  申请人：Abbott Laboratories

  公开号：EP2421845B1

  公开（公告）日：2013-04-17
• HETEROCYCLIC ANTIVIRAL COMPOUNDS
  申请人：F.Hoffmann-La Roche AG

  公开号：EP2603501B1

  公开（公告）日：2014-05-14
• Antiviral Compounds And Uses Thereof
  申请人：Rockway Todd W.

  公开号：US20120100104A1

  公开（公告）日：2012-04-26

  This invention relates to: (a) compounds and salts thereof that, inter alia, inhibit HCV; (b) intermediates useful for the preparation of such compounds and salts; (c) compositions comprising such compounds and salts; (d) methods for preparing such intermediates, compounds, salts, and compositions; (e) methods of use of such compounds, salts, and compositions; and (f) kits comprising such compounds, salts, and compositions.