2-(5-Bromo-1-cyclopropylmethyl-2,2-dioxo-1,4-dihydro-2H-2λ⁶-benzo[1,2,6]thiadiazin-3-yl)-N-hydroxy-acetamide

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 2-(5-Bromo-1-cyclopropylmethyl-2,2-dioxo-1,4-dihydro-2H-2λ⁶-benzo[1,2,6]thiadiazin-3-yl)-N-hydroxy-acetamide
• 英文别名: 2-[5-bromo-1-(cyclopropylmethyl)-2,2-dioxo-4H-2lambda6,1,3-benzothiadiazin-3-yl]-N-hydroxyacetamide；2-[5-bromo-1-(cyclopropylmethyl)-2,2-dioxo-4H-2λ6,1,3-benzothiadiazin-3-yl]-N-hydroxyacetamide
• 化学式: C₁₃H₁₆BrN₃O₄S
• 分子量: 390.258
• InChiKey: PFNDNHVINJSDGW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  22
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  98.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (5-bromo-1-cyclopropylmethyl-2,2-dioxo-1,4-dihydro-2H-2λ⁶-benzo[1,2,6]thiadiazin-3-yl)-acetic acid ethyl ester 在 氢氧化钾 、 盐酸羟胺 作用下， 以 四氢呋喃 为溶剂， 反应 2.0h， 以60%的产率得到2-(5-Bromo-1-cyclopropylmethyl-2,2-dioxo-1,4-dihydro-2H-2λ⁶-benzo[1,2,6]thiadiazin-3-yl)-N-hydroxy-acetamide
  参考文献：
  名称：

  2-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)- and 2-(2,2-Dioxo-1,4-dihydro-2H-2λ⁶-benzo[1,2,6]thiadiazin-3-yl)-N-hydroxy-acetamides as Potent and Selective Peptide Deformylase Inhibitors

  摘要：

  Potent, selective, and structurally new inhibitors of the Fe(II) enzyme Escherichia coli peptide deformylase (PDF) were obtained by rational optimization of the weakly binding screening hit (5-chloro-2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-acetic acid hydrazide (1). Three-dimensional structural information, gathered from Ni-PDF complexed with 1, suggested the preparation of two series of related hydroxamic acid analogues, 2-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)hydroxy-acetamides (A) and 2-(2,2-dioxo-1,4-dihydro-2H-2 lambda (6)-benzo[1,2,6] thiadiazin-3-yl)-N-hydroxy-acetamides (B), among which potent PDF inhibitors (37, 42, and 48) were identified. Moreover, two selected compounds, one from each series, 36 and 41, showed good selectivity for PDF over several endoproteases including matrix metalloproteases. However, these compounds showed only weak antibacterial activity.

  DOI：

  10.1021/jm000352g

文献信息

• 2-(2-Oxo-1,4-dihydro-2<i>H</i>-quinazolin-3-yl)- and 2-(2,2-Dioxo-1,4-dihydro-2<i>H</i>-2λ⁶-benzo[1,2,6]thiadiazin-3-yl)-<i>N</i>-hydroxy-acetamides as Potent and Selective Peptide Deformylase Inhibitors
  作者：Christian Apfel、David W. Banner、Daniel Bur、Michel Dietz、Christian Hubschwerlen、Hans Locher、Frédéric Marlin、Raffaello Masciadri、Wolfgang Pirson、Henri Stalder

  DOI：10.1021/jm000352g

  日期：2001.6.1

  Potent, selective, and structurally new inhibitors of the Fe(II) enzyme Escherichia coli peptide deformylase (PDF) were obtained by rational optimization of the weakly binding screening hit (5-chloro-2-oxo-1,4-dihydro-2H-quinazolin-3-yl)-acetic acid hydrazide (1). Three-dimensional structural information, gathered from Ni-PDF complexed with 1, suggested the preparation of two series of related hydroxamic acid analogues, 2-(2-oxo-1,4-dihydro-2H-quinazolin-3-yl)hydroxy-acetamides (A) and 2-(2,2-dioxo-1,4-dihydro-2H-2 lambda (6)-benzo[1,2,6] thiadiazin-3-yl)-N-hydroxy-acetamides (B), among which potent PDF inhibitors (37, 42, and 48) were identified. Moreover, two selected compounds, one from each series, 36 and 41, showed good selectivity for PDF over several endoproteases including matrix metalloproteases. However, these compounds showed only weak antibacterial activity.