N-methyl-2-(4-(8-nitro-4-oxo-6-(trifluoromethyl)-4H-benzo[e][1,3]thiazin-2-yl)piperazin-1-yl)-N-phenylacetamide | 1383531-32-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二嗪烷类
• 英文名称: N-methyl-2-(4-(8-nitro-4-oxo-6-(trifluoromethyl)-4H-benzo[e][1,3]thiazin-2-yl)piperazin-1-yl)-N-phenylacetamide
• 英文别名: N-methyl-2-[4-[8-nitro-4-oxo-6-(trifluoromethyl)-1,3-benzothiazin-2-yl]piperazin-1-yl]-N-phenyl-acetamide；N-methyl-2-[4-[8-nitro-4-oxo-6-(trifluoromethyl)-1,3-benzothiazin-2-yl]piperazin-1-yl]-N-phenylacetamide
• CAS: 1383531-32-5
• 化学式: C₂₂H₂₀F₃N₅O₄S
• 分子量: 507.493
• InChiKey: LJMIHUUIDCUYFU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  35
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  127
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  对氯三氟甲苯 在 N,N-二甲基甲酰胺 ammonium hydroxide 、 正丁基锂 、 氯化亚砜 、 四甲基乙二胺 、 硫酸 、 硝酸 、 sodium hydroxide 作用下， 以 四氢呋喃 、 hexanes 、 乙醇 、 氯仿 、 二甲基亚砜 、 乙腈 为溶剂， 反应 6.51h， 生成 N-methyl-2-(4-(8-nitro-4-oxo-6-(trifluoromethyl)-4H-benzo[e][1,3]thiazin-2-yl)piperazin-1-yl)-N-phenylacetamide
  参考文献：
  名称：

  [EN] NOVEL ANTI-TUBERCULOSIS AGENTS
  [FR] NOUVEAUX AGENTS ANTI-TUBERCULOSE

  摘要：

  化合物的新型苯并噻唑酮衍生物（I）或其药学上可接受的盐或溶剂已被发现对结核分枝杆菌株具有有效作用，因此可能在结核病的治疗中有用（I）其中，EWG（电子吸引基团）= N02、CN、CF3、F、CI、Br、OCF3、OH、OR、OCHF2、COOR，其中R为氢，或直链或支链的C1-C4烷基基团，X = 一个键，或者是一个直链或支链的C1-C4烷基烃基团；Y = 一个键，或者是一个直链或支链的C1-C4烷基烃基团；其中X或Y中的任一者是一个键，另一个是一个Ci-C4-烷基烃基团，Z = N或C，n = 1或2；R1 = 氢，一个直链或支链的C1-C6烷基基团，或一个C3-C6环烷基团，它可以被来自F、CI、Br、I或C1-C4烷氧的基团取代；R2 = 苯基、萘基或噻吩基，每个基团可以未取代或取代一个或多个取代基，这些基团可以相同或不同于彼此，选自F、CI、Br、I、CN、NO2或直链或支链的C1-C6烷基或苯基基团，它可以被来自F、CI、Br、I或C1-C4烷氧的基团取代。

  公开号：

  WO2012085654A1

文献信息

• [EN] NOVEL ANTI-TUBERCULOSIS AGENTS<br/>[FR] NOUVEAUX AGENTS ANTI-TUBERCULOSE
  申请人：UNIV QUEENSLAND

  公开号：WO2012085654A1

  公开（公告）日：2012-06-28

  Novel benzothiazinone derivatives of formula (I) or a pharmaceutically acceptable salt or solvate thereof have been found to be effective against Mycobacterium tuberculosis strains and may thus be useful in the treatment of tuberculosis (I) wherein, EWG (electron withdrawing group) = N02, CN, CF3, F, CI, Br, OCF3, OH, OR, OCHF2, COOR, wherein R is hydrogen, or a straight or branched C1-C4 alkyl group, X = a bond, or a straight or branched C1-C4 alkylene group; Y = a bond, or a straight or branched C1-C4 alkylene group; wherein either one of X or Y is a bond and the other is a Ci-C4-alkylene group, Z = N or C, n = 1 or 2; R1 = hydrogen, a straight or branched C1-C6 alkyl group, or a C3-C6 cycloalkyl group, which may be substituted with a group selected from F, CI, Br, I or a C1-C4 alkoxy; R2 = a phenyl group, a naphthyl group or a thienyl group, each of which may be unsubstituted or substituted with one or more substituent(s) which may be the same or different from each other, selected from the group consisting of F, CI, Br, I, CN, NO2, or a straight or branched C1-C6 alkyl or phenyl group, which may be substituted with a group selected from F, CI, Br, I, or C1-C4 alkoxy.

  化合物的新型苯并噻唑酮衍生物（I）或其药学上可接受的盐或溶剂已被发现对结核分枝杆菌株具有有效作用，因此可能在结核病的治疗中有用（I）其中，EWG（电子吸引基团）= N02、CN、CF3、F、CI、Br、OCF3、OH、OR、OCHF2、COOR，其中R为氢，或直链或支链的C1-C4烷基基团，X = 一个键，或者是一个直链或支链的C1-C4烷基烃基团；Y = 一个键，或者是一个直链或支链的C1-C4烷基烃基团；其中X或Y中的任一者是一个键，另一个是一个Ci-C4-烷基烃基团，Z = N或C，n = 1或2；R1 = 氢，一个直链或支链的C1-C6烷基基团，或一个C3-C6环烷基团，它可以被来自F、CI、Br、I或C1-C4烷氧的基团取代；R2 = 苯基、萘基或噻吩基，每个基团可以未取代或取代一个或多个取代基，这些基团可以相同或不同于彼此，选自F、CI、Br、I、CN、NO2或直链或支链的C1-C6烷基或苯基基团，它可以被来自F、CI、Br、I或C1-C4烷氧的基团取代。
• Development of Predictive Classification Models for Whole Cell Antimycobacterial Activity of Benzothiazinones
  作者：Sebastian Schieferdecker、Freddy A. Bernal、K. Philip Wojtas、François Keiff、Yan Li、Hans-Martin Dahse、Florian Kloss

  DOI：10.1021/acs.jmedchem.2c00098

  日期：2022.5.12

  against Mycobacterium tuberculosis. However, relationships between their structural properties and whole cell activity remain poorly predictable. Herein, we present the synthesis and antimycobacterial evaluation of a diverse set of BTZs. High potency was predominantly achieved by piperidine and piperazine substitutions, whereupon three compounds were identified as promising candidates, showing preferable

  硝基苯并噻嗪酮 (BTZ) 是一类非常有效的抗结核分枝杆菌的抗生素. 然而，它们的结构特性和全细胞活性之间的关系仍然很难预测。在此，我们介绍了多种 BTZ 的合成和抗分枝杆菌评估。高效力主要通过哌啶和哌嗪取代来实现，因此三种化合物被确定为有希望的候选物，显示出较好的代谢稳定性。效力和计算的结合能之间缺乏相关性表明靶抑制不是获得合适的抗分枝杆菌剂的唯一要求。相比之下，通过广泛验证的机器学习模型成功地完成了全细胞活动类别的预测。通过对大量报告的 BTZ 进行 >70% 的正确类别预测，进一步验证了卓越模型的性能。
• Identification of Antitubercular Benzothiazinone Compounds by Ligand-Based Design
  作者：Tomislav Karoli、Bernd Becker、Johannes Zuegg、Ute Möllmann、Soumya Ramu、Johnny X. Huang、Matthew A. Cooper

  DOI：10.1021/jm3008882

  日期：2012.9.13

  1,3-Benzothiazin-4-ones (BTZs) are a novel class of TB drug candidates with potent activity against M. tuberculosis. An in silico ligand-based model based on structure-activity data from 170 BTZ compounds was used to design a new series. Compounds were tested against a panel of mycobacterial strains and were profiled for cytotoxicity, stability, and antiproliferative effects. Several of the compounds showed improved activity against MDR-TB while retaining low toxicity with higher microsomal, metabolic, and plasma stability.
• Benzothiazinone compounds and their use as anti-tuberculosis agents
  申请人：The University of Queensland

  公开号：EP2468746A1

  公开（公告）日：2012-06-27

  Novel benzothiazinone derivatives of formula (I) or a pharmaceutically acceptable salt or solvate thereof have been found to be effective against Mycobacterium tuberculosis strains and may thus be useful in the treatment of tuberculosis: wherein EWG (electron withdrawing group) = NO2, CN, CF3, F, Cl, Br, OCF3, OH, OR, OCHF2, COOR, wherein R is hydrogen, or a straight or branched C1-C4 alkyl group, X a bond, or a straight or branched C1-C4 alkylene group; Y = a bond, or a straight or branched C1-C4 alkylene group; wherein either one of X or Y is a bond and the other is a C1-C4- alkylene group, Z = N or C, n = 1 or 2; R1 = hydrogen, a straight or branched C1-C6 alkyl group, or a C3-C6 cycloalkyl group, which may be substituted with a group selected from F, Cl, Br, I or a C1-C4 alkoxy ; R2 = a phenyl group, a naphthyl group or a thienyl group, each of which may be unsubstituted or substituted with one or more substituent(s) which may be the same or different from each other, selected from the group consisting of F, Cl, Br, I, CN, NO2, or a straight or branched C1-C6 alkyl or phenyl group, which may be substituted with a group selected from F, Cl, Br, I, or C1-C4 alkoxy.

  化合物（I）的新型苯并噻唑酮衍生物或其药学上可接受的盐或溶剂已被发现对结核分枝杆菌菌株有效，并因此可能在结核病治疗中有用：其中EWG（电子提取基团）= NO2、CN、CF3、F、Cl、Br、OCF3、OH、OR、OCHF2、COOR，其中R为氢，或直链或支链C1-C4烷基；X为键，或直链或支链C1-C4亚烷基；Y = 键，或直链或支链C1-C4亚烷基；其中X或Y中的一个为键，另一个为C1-C4亚烷基，Z = N或C，n = 1或2；R1 = 氢，直链或支链C1-C6烷基，或C3-C6环烷基，可用F、Cl、Br、I或C1-C4烷氧基中选择的基团取代；R2 = 苯基，萘基或噻吩基，每个基团可以未取代或取代一个或多个取代基（s），其可相同或不同于来自F、Cl、Br、I、CN、NO2或直链或支链C1-C6烷基或苯基的基团，可用F、Cl、Br、I或C1-C4烷氧基中选择的基团取代。