N-[3-[(2S)-2-tert-butyl-1-[(4-fluorophenyl)methyl]-3-hydroxy-5-oxo-2H-pyrrol-4-yl]-2-methyl-1,1-dioxo-4H-1$l^{6},4-benzothiazin-7-yl]methanesulfonamide | 947241-79-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: N-[3-[(2S)-2-tert-butyl-1-[(4-fluorophenyl)methyl]-3-hydroxy-5-oxo-2H-pyrrol-4-yl]-2-methyl-1,1-dioxo-4H-1$l^{6},4-benzothiazin-7-yl]methanesulfonamide
• 英文别名: N-[3-[(2S)-2-tert-butyl-1-[(4-fluorophenyl)methyl]-3-hydroxy-5-oxo-2H-pyrrol-4-yl]-2-methyl-1,1-dioxo-4H-1λ6,4-benzothiazin-7-yl]methanesulfonamide
• CAS: 947241-79-4
• 化学式: C₂₅H₂₈FN₃O₆S₂
• 分子量: 549.644
• InChiKey: ZYDROKLLHXOYDI-HSZRJFAPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  37
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  150
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  (S)-3-(7-amino-2-methyl-1,1-dioxido-4H-benzo[b][1,4]thiazin-3-yl)-5-(tert-butyl)-1-(4-fluorobenzyl)-4-hydroxy-1,5-dihydro-2H-pyrrol-2-one 、 甲基磺酰氯 在 吡啶 作用下， 以72%的产率得到N-[3-[(2S)-2-tert-butyl-1-[(4-fluorophenyl)methyl]-3-hydroxy-5-oxo-2H-pyrrol-4-yl]-2-methyl-1,1-dioxo-4H-1$l^{6},4-benzothiazin-7-yl]methanesulfonamide
  参考文献：
  名称：

  Non-nucleoside inhibitors of HCV polymerase NS5B. Part 3: Synthesis and optimization studies of benzothiazine-substituted tetramic acids

  摘要：

  Benzothiazine-substituted tetramic acids were discovered as highly potent non-nucleoside inhibitors of HCV NS5B polymerase. X-ray crystallography studies confirmed the binding mode of these inhibitors with HCV NS5B polymerase. Rational optimization of time dependent inactivation of CYP 3A4 and clearance was accomplished by incorporation of electron-withdrawing groups to the benzothiazine core. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2009.08.023

文献信息

• Heterocyclic antiviral compounds
  申请人：Fell Bradford Jay

  公开号：US20080095739A1

  公开（公告）日：2008-04-24

  Compounds having the formula Ia or Ib wherein R 1 , R 2 , R 3 and R 4 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Ia或Ib式中定义的R1、R2、R3和R4的化合物是丙型肝炎病毒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。
• HETEROCYCLIC ANTIVIRAL COMPOUNDS
  申请人：F.Hoffmann-La Roche AG

  公开号：EP1987027B1

  公开（公告）日：2010-12-15
• US7531534B2
  申请人：——

  公开号：US7531534B2

  公开（公告）日：2009-05-12
• Non-nucleoside inhibitors of HCV polymerase NS5B. Part 3: Synthesis and optimization studies of benzothiazine-substituted tetramic acids
  作者：Javier de Vicente、Robert T. Hendricks、David B. Smith、Jay B. Fell、John Fischer、Stacey R. Spencer、Peter J. Stengel、Peter Mohr、John E. Robinson、James F. Blake、Ramona K. Hilgenkamp、Calvin Yee、Junping Zhao、Todd R. Elworthy、Jahari Tracy、Elbert Chin、Jim Li、Al Lui、Beihan Wang、Connie Oshiro、Seth F. Harris、Manjiri Ghate、Vincent J.P. Leveque、Isabel Najera、Sophie Le Pogam、Sonal Rajyaguru、Gloria Ao-Ieong、Ludmila Alexandrova、Bill Fitch、Michael Brandl、Mohammad Masjedizadeh、Shao-yong Wu、Steve de Keczer、Tatyana Voronin

  DOI：10.1016/j.bmcl.2009.08.023

  日期：2009.10

  Benzothiazine-substituted tetramic acids were discovered as highly potent non-nucleoside inhibitors of HCV NS5B polymerase. X-ray crystallography studies confirmed the binding mode of these inhibitors with HCV NS5B polymerase. Rational optimization of time dependent inactivation of CYP 3A4 and clearance was accomplished by incorporation of electron-withdrawing groups to the benzothiazine core. (C) 2009 Elsevier Ltd. All rights reserved.