1-(3-bromophenyl)-4-methyl-1,4-dihydropyrazolo[4,3-c]-[1,2]benzothiazine-3-carboxylic acid 5,5-dioxide | 1588396-15-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 1-(3-bromophenyl)-4-methyl-1,4-dihydropyrazolo[4,3-c]-[1,2]benzothiazine-3-carboxylic acid 5,5-dioxide
• CAS: 1588396-15-9
• 化学式: C₁₇H₁₂BrN₃O₄S
• 分子量: 434.27
• InChiKey: JLZJRPQEFRUZOM-UHFFFAOYSA-N

物化性质

• 熔点：
  228-230 °C
• 沸点：
  679.3±65.0 °C(predicted)
• 密度：
  1.77±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.14
• 重原子数：
  26.0
• 可旋转键数：
  2.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.06
• 拓扑面积：
  92.5
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  1-(3-bromophenyl)-4-methyl-1,4-dihydropyrazolo[4,3-c]-[1,2]benzothiazine-3-carboxylic acid 5,5-dioxide 在 氯化亚砜 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 25.0h， 生成 1-(3-bromophenyl)-4-methyl-N-{4-[(methylsulfonyl)amino]-phenyl}-1,4-dihydropyrazolo[4,3-c][1,2]benzothiazine-3-carboxamide 5,5-dioxide
  参考文献：
  名称：

  New Pyrazolobenzothiazine Derivatives as Hepatitis C Virus NS5B Polymerase Palm Site I Inhibitors

  摘要：

  We have previously identified the pyrazolobenzothiazine scaffold as a promising chemotype against hepatitis C virus (HCV) NS5B polymerase, a validated and promising anti-HCV target. Herein we describe the design, synthesis, enzymatic, and cellular characterization of new pyrazolobenzothiazines as anti-HCV inhibitors. The binding site for a representative derivative was mapped to NS5B palm site 1 employing a mutant counterscreen assay, thus validating our previous in silico predictions. Derivative 2b proved to be the best selective anti-HCV derivative within the new series, exhibiting a IC50 of 7.9 mu M against NS5B polymerase and antiviral effect (EC50 = 8.1 mu M; EC90 = 23.3 mu M) coupled with the absence of any antimetabolic effect (CC50 > 224 mu M; SI > 28) in a cell based HCV replicon system assay. Significantly, microscopic analysis showed that, unlike the parent compounds, derivative 2b did not show any significant cell morphological alterations. Furthermore, since most of the pyrazolobenzothiazines tested altered cell morphology, this undesired aspect was further investigated by exploring possible perturbation of lipid metabolism during compound treatment.

  DOI：

  10.1021/jm401688h
• 作为产物：
  描述：

  methyl 1-(3-bromophenyl)-4-methyl-1,4-dihydropyrazolo-[4,3-c][1,2]benzothiazine-3-carboxylate 5,5-dioxide 在 水 、 sodium hydroxide 作用下， 以 甲醇 为溶剂， 反应 1.0h， 以90%的产率得到1-(3-bromophenyl)-4-methyl-1,4-dihydropyrazolo[4,3-c]-[1,2]benzothiazine-3-carboxylic acid 5,5-dioxide
  参考文献：
  名称：

  New Pyrazolobenzothiazine Derivatives as Hepatitis C Virus NS5B Polymerase Palm Site I Inhibitors

  摘要：

  We have previously identified the pyrazolobenzothiazine scaffold as a promising chemotype against hepatitis C virus (HCV) NS5B polymerase, a validated and promising anti-HCV target. Herein we describe the design, synthesis, enzymatic, and cellular characterization of new pyrazolobenzothiazines as anti-HCV inhibitors. The binding site for a representative derivative was mapped to NS5B palm site 1 employing a mutant counterscreen assay, thus validating our previous in silico predictions. Derivative 2b proved to be the best selective anti-HCV derivative within the new series, exhibiting a IC50 of 7.9 mu M against NS5B polymerase and antiviral effect (EC50 = 8.1 mu M; EC90 = 23.3 mu M) coupled with the absence of any antimetabolic effect (CC50 > 224 mu M; SI > 28) in a cell based HCV replicon system assay. Significantly, microscopic analysis showed that, unlike the parent compounds, derivative 2b did not show any significant cell morphological alterations. Furthermore, since most of the pyrazolobenzothiazines tested altered cell morphology, this undesired aspect was further investigated by exploring possible perturbation of lipid metabolism during compound treatment.

  DOI：

  10.1021/jm401688h