6H-quino[3,2-b]benzo[1,4]thiazine | 158438-85-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 6H-quino[3,2-b]benzo[1,4]thiazine
• 英文别名: 6H-quinobenzothiazine；6H-quinolino[3,2-b][1,4]benzothiazine
• CAS: 158438-85-8
• 化学式: C₁₅H₁₀N₂S
• 分子量: 250.324
• InChiKey: ZJENZHUPPZMFPM-UHFFFAOYSA-N

物化性质

• 熔点：
  169-170 °C
• 沸点：
  471.7±45.0 °C(predicted)
• 密度：
  1.36±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  18
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  50.2
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  6H-quino[3,2-b]benzo[1,4]thiazine 在 sodium hydride 、 sodium carbonate 、 肼 作用下， 以 正己烷 、 二氯甲烷 、 水 、 甲苯 为溶剂， 反应 50.5h， 生成 6-ethoxycarbonylaminobutylquinobenzothiazine
  参考文献：
  名称：

  Synthesis and selected immunological properties of substituted quino[3,2-b]benzo[1,4]thiazines

  摘要：

  A new type of azaphenothiazines - tetracyclic quino[3,2-b]benzo[1,4]thiazines, possessing common substituents (H, CH3, Cl, Br, F, CF3, SCH3) in positions 8-10 and pharmacophoric aminoalkyl substituents in position 6, were-obtained from-diquinodithiin and 2,2'-dichloro-3,3'-diquinolinyl disulfide in several-step syntheses. Sixty one compounds, grouped as the 6H, 6-dialkylaminoalkyl, 6-acylaminoalkyl and sulfonylaminoalkyl derivatives, were tested for cytotoxicity, their effects on phytohemagglutin A (PHA)-induced proliferative response of human peripheral blood mononuclear cells (PBMC) and lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) production by these cells. The compounds exhibited differential inhibitory activities in these tests and significantly varied in terms of cytotoxicity. The most promising compounds were tested for growth inhibition of leukemia L-1210 cells, colon cancer SV-948 cells and epidermal carcinoma A-341 cells. The most active compounds exhibited anticancer activity against these cell lines comparable to that of cisplatin. The structure-activity relationship of the compounds were discussed. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.02.023
• 作为产物：
  描述：

  5,12-diaza-6,13-dithiapentacene 、 aniline hydrochloride 反应 4.0h， 以52%的产率得到6H-quino[3,2-b]benzo[1,4]thiazine
  参考文献：
  名称：

  Diquino-1,4-dithiin 和 2,2'-Dichloro-3,3'-diquinolinyl Disulfide 合成 Quinobenzo-1,4-thiazines

  摘要：

  合成新型四环氮杂吩噻嗪，6-, 8-, 9- 和 10-取代的 quinobenzo-1,4-thiazines (benzo[b]-1-azaphenothiazines) (5) 和 (10), 从diquino-1,4-dithiin (5,12-diaza-6,13-​​dithiapentacene) (2) 通过 1,4-dithiin 开环和 1,4-thiazine 与盐酸苯胺 (8)·HCl 发生融合反应闭环。当 2,2'-二氯-3,3'-二喹啉基二硫化物 (9) 与苯胺 (8) 在 MEDG 中反应时，获得了更好的结果。选择的 6H-quinobenzo-1,4-thiazines (5a) (5c) 和 (5g) 通过使用烷基卤化物的 N-烷基化转化为 6-烷基衍生物 (10a-10n)。6-甲基衍生物（10a）的同核NOE实验证实产物结构为醌[3,2-b]苯并[1,4]噻嗪。

  DOI：

  10.3987/com-09-11736

文献信息

• Synthesis and biological evaluation of novel propargylquinobenzothiazines and their derivatives as potential antiproliferative, anti-inflammatory, and anticancer agents
  作者：Małgorzata Jeleń、Krystian Pluta、Michał Zimecki、Beata Morak-Młodawska、Jolanta Artym、Maja Kocięba、Iwona Kochanowska

  DOI：10.1080/14756366.2016.1205046

  日期：2016.11.3

  containing the quinoline ring, 8-10-substituted 6H-quinobenzothiazines and 6H-diquinothiazine were transformed into new 6-propargyl and 6-dialkylaminobutynyl derivatives containing the triple bond. Most of them displayed strong antiproliferative actions against human peripheral blood mononuclear cells (PBMC) stimulated with phytohemagglutinin A (PHA), strongly suppressed lipopolysaccharide (LPS)-induced

  将含有喹啉环的氮杂吩噻嗪，8-10-取代的6H-喹啉苯并噻嗪和6H-二喹噻嗪转化为含有三键的新的6-炔丙基和6-二烷基氨基丁炔基衍生物。它们中的大多数对由植物血凝素A（PHA）刺激的人外周血单个核细胞（PBMC）表现出强大的抗增殖作用，通过全血人细胞培养物强烈抑制脂多糖（LPS）诱导的TNF-α产生，并且具有较低的细胞毒性。具有在位置9处的溴，三氟甲基和甲硫基的三个炔丙基喹啉苯并噻嗪和炔丙基二喹硫噻嗪在对抗L-1210和SW-948肿瘤方面表现出与顺铂相当的作用。研究表明6-炔丙基-9-三氟甲基喹苯并噻嗪在Jurkat细胞中阻断caspase 3的表达并抑制caspase 8和9的表达，表明其可能的作用机理。这些衍生物可能是有希望的，潜在的用于治疗肿瘤疾病和自身免疫性疾病的疗法。
• Synthesis of quinoline/naphthalene-containing azaphenothiazines and their potent in vitro antioxidant properties
  作者：Małgorzata Jeleń、Eugenia I. Bavavea、Maria Pappa、Angeliki P. Kourounakis、Beata Morak-Młodawska、Krystian Pluta

  DOI：10.1007/s00044-014-1247-y

  日期：2015.4

  New tetracyclic and pentacyclic azaphenothiazines containing one or two quinoline rings instead of benzene rings were obtained in the original reactions of isomeric diquinodithiins, dichlorodiquinolinyl sulfides, and disulfide with aromatic amines. The type of ring fusion in the azaphenothiazine system was concluded from the H-1 NMR spectra. The obtained azaphenothiazines were evaluated in vitro for their antioxidant activity on rat hepatic microsomal membranes for protection of non-enzymatic lipid peroxidation promoted by the Fe2+/ascorbic acid redox system. Most compounds exhibited a very significant antioxidant activity with IC50 values between 1 and 23 mu M. The degree of antioxidant activity depends on the lipophilicity and molecular size as well as the (non)substitution of the thiazine nitrogen atom and type of ring system fusion. It is the first time to our knowledge that azaphenothiazines are shown to exhibit such potent antioxidant activity.
• Synthesis and selected immunological properties of substituted quino[3,2-b]benzo[1,4]thiazines
  作者：Małgorzata Jeleń、Krystian Pluta、Michał Zimecki、Beata Morak-Młodawska、Jolanta Artym、Maja Kocięba

  DOI：10.1016/j.ejmech.2013.02.023

  日期：2013.5

  A new type of azaphenothiazines - tetracyclic quino[3,2-b]benzo[1,4]thiazines, possessing common substituents (H, CH3, Cl, Br, F, CF3, SCH3) in positions 8-10 and pharmacophoric aminoalkyl substituents in position 6, were-obtained from-diquinodithiin and 2,2'-dichloro-3,3'-diquinolinyl disulfide in several-step syntheses. Sixty one compounds, grouped as the 6H, 6-dialkylaminoalkyl, 6-acylaminoalkyl and sulfonylaminoalkyl derivatives, were tested for cytotoxicity, their effects on phytohemagglutin A (PHA)-induced proliferative response of human peripheral blood mononuclear cells (PBMC) and lipopolysaccharide (LPS)-induced tumor necrosis factor alpha (TNF-alpha) production by these cells. The compounds exhibited differential inhibitory activities in these tests and significantly varied in terms of cytotoxicity. The most promising compounds were tested for growth inhibition of leukemia L-1210 cells, colon cancer SV-948 cells and epidermal carcinoma A-341 cells. The most active compounds exhibited anticancer activity against these cell lines comparable to that of cisplatin. The structure-activity relationship of the compounds were discussed. (C) 2013 Elsevier Masson SAS. All rights reserved.
• Synthesis of Quinobenzo-1,4-thiazines from Diquino-1,4-dithiin and 2,2’-Dichloro-3,3’-diquinolinyl Disulfide
  作者：Krystian Pluta、Małgorzata Jeleń

  DOI：10.3987/com-09-11736

  日期：——

  10-substituted quinobenzo-1,4-thiazines (benzo[b]-1-azaphenothiazines) (5) and (10), has been worked out from diquino-1,4-dithiin (5,12-diaza-6,13-dithiapentacene) (2) as fusion reactions with aniline hydrochlorides (8)·HCl via the 1,4-dithiin ring opening and the 1,4-thiazine ring closure. The better results were obtained when 2,2'-dichloro-3,3'-diquinolinyl disulfide (9) reacted with anilines (8) in MEDG

  合成新型四环氮杂吩噻嗪，6-, 8-, 9- 和 10-取代的 quinobenzo-1,4-thiazines (benzo[b]-1-azaphenothiazines) (5) 和 (10), 从diquino-1,4-dithiin (5,12-diaza-6,13-​​dithiapentacene) (2) 通过 1,4-dithiin 开环和 1,4-thiazine 与盐酸苯胺 (8)·HCl 发生融合反应闭环。当 2,2'-二氯-3,3'-二喹啉基二硫化物 (9) 与苯胺 (8) 在 MEDG 中反应时，获得了更好的结果。选择的 6H-quinobenzo-1,4-thiazines (5a) (5c) 和 (5g) 通过使用烷基卤化物的 N-烷基化转化为 6-烷基衍生物 (10a-10n)。6-甲基衍生物（10a）的同核NOE实验证实产物结构为醌[3,2-b]苯并[1,4]噻嗪。