6-氯-2-(甲硫基)-8-硝基-4H-苯并[E][1,3]噻嗪-4-酮 | 1377240-43-1

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 中文名称: 6-氯-2-(甲硫基)-8-硝基-4H-苯并[E][1,3]噻嗪-4-酮
• 英文名称: 6-Chloro-2-(methylthio)-8-nitro-4H-benzo[e][1,3]thiazin-4-one
• 英文别名: 6-chloro-2-methylsulfanyl-8-nitro-1,3-benzothiazin-4-one
• CAS: 1377240-43-1
• 化学式: C₉H₅ClN₂O₃S₂
• 分子量: 288.735
• InChiKey: BRQPRDBHOUMRBA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  126
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  6-氯-2-(甲硫基)-8-硝基-4H-苯并[E][1,3]噻嗪-4-酮 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成 6-chloro-2-[4-(2-methylquinoline-4-carbonyl)piperazin-1-yl]-8-nitro-4H-benzo[e][1,3]thiazin-4-one
  参考文献：
  名称：

  Bioevaluation of quinoline‐4‐carbonyl derivatives of piperazinyl‐benzothiazinones as promising antimycobacterial agents

  摘要：

  AbstractThe quinoline moiety remains a privileged antitubercular (anti‐TB) pharmacophore, whereas 8‐nitrobenzothiazinones are emerging potent antimycobacterial agents with two investigational candidates in the clinical pipeline. Herein, we report the synthesis and bioevaluation of 30 piperazinyl‐benzothiazinone‐based quinoline hybrids as prospective anti‐TB agents. Preliminary evaluation revealed 24/30 compounds exhibiting substantial activity (minimum inhibitory concentration [MIC] = 0.06–1 µg/ml) against Mycobacterium tuberculosis (Mtb) H37Rv. Cytotoxicity analysis against Vero cells found these to be devoid of any significant toxicity, with the majority displaying a selectivity index of >80. Furthermore, potent nontoxic compounds, when screened against clinical isolates of drug‐resistant Mtb strains, demonstrated equipotent inhibition with MIC values of 0.03–0.25 µg/ml. A time‐kill study identified a lead compound exhibiting concentration‐dependent bactericidal activity, with 10× MIC completely eliminating Mtb bacilli within 7 days. Along with acceptable aqueous solubility and microsomal stability, the optimum active compounds of the series manifested all desirable traits of a promising antimycobacterial candidate.

  DOI：

  10.1002/ardp.202200168
• 作为产物：
  描述：

  2,5-二氯-3-硝基苯甲酸 在 氯化亚砜 、 sodium hydroxide 作用下， 以 氯仿 、 二甲基亚砜 为溶剂， 反应 7.5h， 生成 6-氯-2-(甲硫基)-8-硝基-4H-苯并[E][1,3]噻嗪-4-酮
  参考文献：
  名称：

  Bioevaluation of quinoline‐4‐carbonyl derivatives of piperazinyl‐benzothiazinones as promising antimycobacterial agents

  摘要：

  AbstractThe quinoline moiety remains a privileged antitubercular (anti‐TB) pharmacophore, whereas 8‐nitrobenzothiazinones are emerging potent antimycobacterial agents with two investigational candidates in the clinical pipeline. Herein, we report the synthesis and bioevaluation of 30 piperazinyl‐benzothiazinone‐based quinoline hybrids as prospective anti‐TB agents. Preliminary evaluation revealed 24/30 compounds exhibiting substantial activity (minimum inhibitory concentration [MIC] = 0.06–1 µg/ml) against Mycobacterium tuberculosis (Mtb) H37Rv. Cytotoxicity analysis against Vero cells found these to be devoid of any significant toxicity, with the majority displaying a selectivity index of >80. Furthermore, potent nontoxic compounds, when screened against clinical isolates of drug‐resistant Mtb strains, demonstrated equipotent inhibition with MIC values of 0.03–0.25 µg/ml. A time‐kill study identified a lead compound exhibiting concentration‐dependent bactericidal activity, with 10× MIC completely eliminating Mtb bacilli within 7 days. Along with acceptable aqueous solubility and microsomal stability, the optimum active compounds of the series manifested all desirable traits of a promising antimycobacterial candidate.

  DOI：

  10.1002/ardp.202200168

文献信息

• [EN] 2-PIPERAZIN-1-YL-4H-1,3-BENZOTHIAZIN-4-ONE DERIVATIVES AND THEIR USE FOR THE TREATMENT OF MAMMALIAN INFECTIONS<br/>[FR] DÉRIVÉS DE 2-PIPÉRAZIN-1-YL-4H-1,3-BENZOTHIAZIN-4-ONE ET LEUR UTILISATION DANS LE TRAITEMENT DES INFECTIONS CHEZ LES MAMMIFÈRES
  申请人：ECOLE POLYTECH

  公开号：WO2012066518A1

  公开（公告）日：2012-05-24

  The present invention relates to new 2-piperazin-1-yl-4H-1,3-benzothiazin- 4-one derivatives and their use for the treatment of mammalian infections caused by bacteria, especially diseases like tuberculosis (TB), Buruli ulcer and leprosy that result from infection with closely related mycobacteria. (I).

  本发明涉及新的2-哌嗪基-4H-1,3-苯并噻唑-4-酮衍生物及其用于治疗由细菌引起的哺乳动物感染，特别是由与结核分枝杆菌密切相关的感染引起的疾病，如肺结核（TB）、布鲁利溃疡和麻风病。