[7-(methanesulfonyl-methyl-amino)-1,1-dioxo-1,4-dihydro-1λ⁶-benzo[1,4]thiazin-3-yl]-acetic acid ethyl ester | 877142-90-0

• 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: [7-(methanesulfonyl-methyl-amino)-1,1-dioxo-1,4-dihydro-1λ⁶-benzo[1,4]thiazin-3-yl]-acetic acid ethyl ester
• 英文别名: [7-(Methanesulfonyl-methyl-amino)-1,1-dioxo-1,4-dihydro-1lambda6-benzo[1,4]thiazin-3-yl]-acetic acid ethyl ester；ethyl 2-[7-[methyl(methylsulfonyl)amino]-1,1-dioxo-4H-1λ6,4-benzothiazin-3-yl]acetate
• CAS: 877142-90-0
• 化学式: C₁₄H₁₈N₂O₆S₂
• 分子量: 374.439
• InChiKey: IKNSFOOTDSGGMD-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.2
• 重原子数：
  24
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  127
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  6-fluoro-1-(4-fluoro-benzyl)-1H-benzo[d][1,3]oxazine-2,4-dione 、 [7-(methanesulfonyl-methyl-amino)-1,1-dioxo-1,4-dihydro-1λ⁶-benzo[1,4]thiazin-3-yl]-acetic acid ethyl ester 在 potassium tert-butylate 作用下， 以 四氢呋喃 为溶剂， 反应 16.0h， 生成 N-{3-[6-fluoro-1-(4-fluoro-benzyl)-4-hydroxy-2-oxo-1,2-dihydro-quinolin-3-yl]-1,1-dioxo-1,4-dihydro-1λ6-benzo[1,4]thiazin-7-yl}-N-methyl-methanesulfonamide
  参考文献：
  名称：

  Non-nucleoside inhibitors of HCV polymerase NS5B. Part 2: Synthesis and structure–activity relationships of benzothiazine-substituted quinolinediones

  摘要：

  A new series of benzothiazine-substituted quinolinediones were evaluated as inhibitors of HCV polymerase NS5B. SAR studies on this series revealed a methyl sulfonamide group as a high affinity feature. Analogues with this group showed submicromolar potencies in the HCV cell based replicon assay. Pharmacokinetic and toxicology studies were also performed on a selected compound (34) to evaluate in vivo properties of this new class of inhibitors of HCV NS5B polymerase.

  DOI：

  10.1016/j.bmcl.2009.05.004
• 作为产物：
  描述：

  6-溴苯并噻唑 在 palladium diacetate 、 4,5-双二苯基膦-9,9-二甲基氧杂蒽 4-二甲氨基吡啶 、 caesium carbonate 、 sodium thiosulfate 、 三乙胺 、 间氯过氧苯甲酸 、 三氟乙酸 、 肼 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 50.0h， 生成 [7-(methanesulfonyl-methyl-amino)-1,1-dioxo-1,4-dihydro-1λ⁶-benzo[1,4]thiazin-3-yl]-acetic acid ethyl ester
  参考文献：
  名称：

  PYRIDAZINONE COMPOUNDS

  摘要：

  该发明涉及吡啶并酮化合物和含有这种化合物的药物组合物，可用于治疗丙型肝炎病毒感染。

  公开号：

  US20080090814A1

文献信息

• 4-(1,1-Dioxo-1,4-dihydro-1λ6-benzo[1,4]thiazin-3-yl)-5-hydroxy-2H-pyridazin-3-ones as potent inhibitors of HCV NS5B polymerase
  作者：David A. Ellis、Julie K. Blazel、Stephen E. Webber、Chinh V. Tran、Peter S. Dragovich、Zhongxiang Sun、Frank Ruebsam、Helen M. McGuire、Alan X. Xiang、Jingjing Zhao、Lian-Sheng Li、Yuefen Zhou、Qing Han、Charles R. Kissinger、Richard E. Showalter、Matthew Lardy、Amit M. Shah、Mei Tsan、Rupal Patel、Laurie A. LeBrun、Ruhi Kamran、Darian M. Bartkowski、Thomas G. Nolan、Daniel A. Norris、Maria V. Sergeeva、Leo Kirkovsky

  DOI：10.1016/j.bmcl.2008.07.014

  日期：2008.8

  4-(1,1-Dioxo-1,4-dihydro-1lambda(6)-benzo[1,4]thiazin-3-yl)-5-hydroxy-2H-pyridazin-3-one analogs were discovered as a novel class of inhibitors of HCV NS5B polymerase. Structure-based design led to the identification of compound 3a that displayed potent inhibitory activities in biochemical and replicon assays (1b IC(50)<10 nM; 1b EC(50)=1.1 nM) as well as good stability toward human liver microsomes (HLM t(1/2)>60 min).
• Non-nucleoside inhibitors of HCV polymerase NS5B. Part 2: Synthesis and structure–activity relationships of benzothiazine-substituted quinolinediones
  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、George Adjabeng、Todd R. Elworthy、Jahari Tracy、Elbert Chin、Jim Li、Beihan Wang、Joe T. Bamberg、Rebecca Stephenson、Connie Oshiro、Seth F. Harris、Manjiri Ghate、Vincent Leveque、Isabel Najera、Sophie Le Pogam、Sonal Rajyaguru、Gloria Ao-Ieong、Ludmila Alexandrova、Susan Larrabee、Michael Brandl、Andrew Briggs、Sunil Sukhtankar、Robert Farrell、Brian Xu

  DOI：10.1016/j.bmcl.2009.05.004

  日期：2009.7

  A new series of benzothiazine-substituted quinolinediones were evaluated as inhibitors of HCV polymerase NS5B. SAR studies on this series revealed a methyl sulfonamide group as a high affinity feature. Analogues with this group showed submicromolar potencies in the HCV cell based replicon assay. Pharmacokinetic and toxicology studies were also performed on a selected compound (34) to evaluate in vivo properties of this new class of inhibitors of HCV NS5B polymerase.
• PYRIDAZINONE COMPOUNDS
  申请人：Ellis David

  公开号：US20080090814A1

  公开（公告）日：2008-04-17

  The invention is directed to pyridazinone compounds and pharmaceutical compositions containing such compounds that are useful in treating infections by hepatitis C virus.

  该发明涉及吡啶并酮化合物和含有这种化合物的药物组合物，可用于治疗丙型肝炎病毒感染。