N-[3-(5-bromo-4-hydroxy-1-isopentyl-2-oxo-1,2-dihydro-3-pyridinyl)-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide | 691362-40-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻二嗪
• 英文名称: N-[3-(5-bromo-4-hydroxy-1-isopentyl-2-oxo-1,2-dihydro-3-pyridinyl)-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
• 英文别名: N-[3-[5-bromo-4-hydroxy-1-(3-methylbutyl)-2-oxopyridin-3-yl]-1,1-dioxo-4H-1λ6,2,4-benzothiadiazin-7-yl]methanesulfonamide
• CAS: 691362-40-0
• 化学式: C₁₈H₂₁BrN₄O₆S₂
• 分子量: 533.424
• InChiKey: HHVBXYOPXVQGOU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.1
• 重原子数：
  31
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  162
• 氢给体数：
  3
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  N-[3-(5-bromo-4-hydroxy-1-isopentyl-2-oxo-1,2-dihydro-3-pyridinyl)-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide 、 tributyl(ethan-1-one)tin 在 bis-triphenylphosphine-palladium(II) chloride 作用下， 以 四氢呋喃 为溶剂， 反应 20.0h， 生成 N-[3-(5-acetyl-4-hydroxy-1-isopentyl-2-oxo-3-pyridyl)-1,1-dioxo-4H-1$l^{6},2,4-benzothiadiazin-7-yl]methanesulfonamide
  参考文献：
  名称：

  Des-A-ring benzothiadiazines: Inhibitors of HCV genotype 1 NS5B RNA-dependent RNA polymerase

  摘要：

  In our program to discover non-nucleoside, small molecule inhibitors of genotype 1 HCV polymerase, we investigated a series of promising analogs based on a benzothiadiazine screening hit that contains an ABCD ring system. After demonstrating that a methylsulfonylamino D-ring substituent increased the enzyme potency into the low nanomolar range, we explored a minimum core required for activity by truncating to a three-ring system. Described herein are the syntheses and structure-activity relationship of a set of inhibitors lacking the A-ring of an ABCD ring system. We observed that small aromatic rings and alkenyl groups appended to the 5-position of the B-ring were optimal, resulting in inhibitors with low nanomolar potencies. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.02.064
• 作为产物：
  描述：

  N-{3-[4-hydroxy-1-(3-methylbutyl)-2-oxo-1,2-dihydropyridin-3-yl]-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl}methanesulfonamide 在 N-bromohydantoin 作用下， 以 四氢呋喃 为溶剂， 生成 N-[3-(5-bromo-4-hydroxy-1-isopentyl-2-oxo-1,2-dihydro-3-pyridinyl)-1,1-dioxido-4H-1,2,4-benzothiadiazin-7-yl]methanesulfonamide
  参考文献：
  名称：

  Des-A-ring benzothiadiazines: Inhibitors of HCV genotype 1 NS5B RNA-dependent RNA polymerase

  摘要：

  In our program to discover non-nucleoside, small molecule inhibitors of genotype 1 HCV polymerase, we investigated a series of promising analogs based on a benzothiadiazine screening hit that contains an ABCD ring system. After demonstrating that a methylsulfonylamino D-ring substituent increased the enzyme potency into the low nanomolar range, we explored a minimum core required for activity by truncating to a three-ring system. Described herein are the syntheses and structure-activity relationship of a set of inhibitors lacking the A-ring of an ABCD ring system. We observed that small aromatic rings and alkenyl groups appended to the 5-position of the B-ring were optimal, resulting in inhibitors with low nanomolar potencies. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.02.064

文献信息

• Anti-infective agents
  申请人：——

  公开号：US20040167123A1

  公开（公告）日：2004-08-26

  The present invention provides an HCV polymerase inhibiting compound having the formula (I) 1 and a composition comprising a therapeutically effective amount of said compound. The present invention also provides a method for inhibiting hepatitis C virus (HCV) polymerase, a method for inhibiting HCV viral replication, and a method for treating or preventing HCV infection. Processes for making said compounds, and synthetic intermediates employed in said processes, are also provided.

  本发明提供了一种具有公式(I)1的HCV聚合酶抑制化合物，以及包含有效治疗量的该化合物的组合物。本发明还提供了用于抑制丙型肝炎病毒（HCV）聚合酶的方法、用于抑制HCV病毒复制的方法以及用于治疗或预防HCV感染的方法。本发明还提供了制造所述化合物的方法以及在这些方法中使用的合成中间体。
• ANTI-INFECTIVE AGENTS
  申请人：ABBOTT LABORATORIES

  公开号：EP1560827B1

  公开（公告）日：2010-12-29
• US7902203B2
  申请人：——

  公开号：US7902203B2

  公开（公告）日：2011-03-08
• Des-A-ring benzothiadiazines: Inhibitors of HCV genotype 1 NS5B RNA-dependent RNA polymerase
  作者：Pamela L. Donner、Qinghua Xie、John K. Pratt、Clarence J. Maring、Warren Kati、Wen Jiang、Yaya Liu、Gennadiy Koev、Sherie Masse、Debra Montgomery、Akhter Molla、Dale J. Kempf

  DOI：10.1016/j.bmcl.2008.02.064

  日期：2008.4

  In our program to discover non-nucleoside, small molecule inhibitors of genotype 1 HCV polymerase, we investigated a series of promising analogs based on a benzothiadiazine screening hit that contains an ABCD ring system. After demonstrating that a methylsulfonylamino D-ring substituent increased the enzyme potency into the low nanomolar range, we explored a minimum core required for activity by truncating to a three-ring system. Described herein are the syntheses and structure-activity relationship of a set of inhibitors lacking the A-ring of an ABCD ring system. We observed that small aromatic rings and alkenyl groups appended to the 5-position of the B-ring were optimal, resulting in inhibitors with low nanomolar potencies. (C) 2008 Elsevier Ltd. All rights reserved.