2-(甲硫基)-6-硝基-4H-苯并[E][1,3]噻嗪-4-酮 | 1344087-75-7

• 分子结构分类: 有机化合物 - 有机杂环化合物
• 中文名称: 2-(甲硫基)-6-硝基-4H-苯并[E][1,3]噻嗪-4-酮
• 英文名称: 2-methylthio-6-nitro-4H-1,3-benzothiazin-4-one
• 英文别名: 2-(Methylthio)-6-nitro-4H-benzo[e][1,3]thiazin-4-one；2-methylsulfanyl-6-nitro-1,3-benzothiazin-4-one
• CAS: 1344087-75-7
• 化学式: C₉H₆N₂O₃S₂
• 分子量: 254.29
• InChiKey: LMLHUTRGCJBSLG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  16
• 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：

  2-(甲硫基)-6-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 2-[4-(6-fluoro-2-methylquinoline-4-carbonyl)piperazin-1-yl]-6-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-氯-5-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 2-(甲硫基)-6-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] PROCESS FOR THE PREPARATION OF 2-AMINO-SUBSTITUTED 1,3-BENZOTHIAZINE-4-ONES<br/>[FR] PROCÉDÉ DE PRÉPARATION DE 1,3-BENZOTHIAZINE-4-ONES 2-AMINO-SUBSTITUÉES
  申请人：MAKAROV VADIM A

  公开号：WO2011132070A1

  公开（公告）日：2011-10-27

  A process for preparing 2-aminosubstituted 1, 3 -benzothiazine- 4 -ones is provided which comprises the following step: Formula (I) wherein Y is halogen; R is independently selected from C1-6-alkyl which may optionally be substituted by halogen, -NO2, halogen, -CHO -COOR4 (wherein R4 is hydrogen or C1-6-alkyl) and -CN; R3 is C1-6-alkyl which may be substituted by halogen; X is halogen; and n is 0 or an integer of 1 to 4; if n is 2, 3 or 4, multiple Rs may be the same or different.

  提供了一种制备2-氨基取代的1,3-苯并噻嗪-4-酮的方法，包括以下步骤：公式（I）其中Y是卤素；R独立地选自C1-6-烷基，该烷基可能被卤素、-NO2、卤素、-CHO、-COOR4（其中R4是氢或C1-6-烷基）和-CN取代；R3是C1-6-烷基，可能被卤素取代；X是卤素；n为0或1至4的整数；如果n为2、3或4，多个R可能相同或不同。
• Process for the preparation of 2-aminosubstituted 1,3-benzothiazine-4-ones
  申请人：Makarov Vadim A.

  公开号：EP2380886A1

  公开（公告）日：2011-10-26

  A process for preparing 2-aminosubstituted 1,3-benzothiazine-4-ones is provided which comprises the following step: wherein Y is halogen; R is independently selected from C1-6-alkyl which may optionally be substituted by halogen, -NO2, halogen, -CHO -COOR4 (wherein R4 is hydrogen or C1-6-alkyl) and -CN; R3 is C1-3-alkyl which may be substituted by halogen; X is halogen; and n is 0 or an integer of 1 to 4; if n is 2, 3 or 4, multiple Rs may be the same or different.

  提供了一种制备2-氨基取代的1,3-苯并噻嗪-4-酮的方法，包括以下步骤：其中Y是卤素；R独立地选自C1-6-烷基，该烷基可以选择性地被卤素、-NO2、卤素、-CHO、-COOR4（其中R4是氢或C1-6-烷基）和-CN取代；R3是C1-3-烷基，可以被卤素取代；X是卤素；n为0或1至4的整数；如果n为2、3或4，多个R可能相同也可能不同。