1,4-diazaphenothiazine | 37693-82-6

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: 1,4-diazaphenothiazine
• 英文别名: 10H-pyrazino[2,3-b][1,4]benzothiazine
• CAS: 37693-82-6
• 化学式: C₁₀H₇N₃S
• 分子量: 201.252
• InChiKey: GKPQIZGCLFSZOF-UHFFFAOYSA-N

物化性质

• 熔点：
  190-192 °C
• 沸点：
  415.4±40.0 °C(Predicted)
• 密度：
  1.359±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  63.1
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,4-diazaphenothiazine 在 水 、 氯 作用下， 以 乙腈 为溶剂， 以63%的产率得到2-苯并噻唑甲酰胺
  参考文献：
  名称：

  1,4-二氮苯哌烯丙嗪的制备及性质

  摘要：

  描述了1,4-二氮杂吩噻嗪的制备和性质，并与1,4-二氮杂吩噻嗪进行了比较。还描述了导致硝基和氯代衍生物以及含硒和含硫杂环的环裂解产物的实验。

  DOI：

  10.1016/0040-4020(80)80141-4
• 作为产物：
  描述：

  2,3-二氯吡嗪 、 2-氨基苯硫醇 在 sodium carbonate 作用下， 以 邻二氯苯 为溶剂， 生成 1,4-diazaphenothiazine
  参考文献：
  名称：

  1,4-二氮杂吩噻嗪化学的某些方面

  摘要：

  喹喔啉[2,3-b] [1,4]苯并噻嗪1及其吡嗪类似物6均给出成对的N-甲基衍生物。的Ñ -甲基化合物2和7与碘苯二氯化物和其它试剂氧化得到亚砜和砜（由某些环取代accompained），但治疗的6与碘代苯dichlorode给出苯并噻唑-2-甲酰胺17。亚硝酸钠在乙酸中对噻嗪6的作用产生3-硝基衍生物25，该取代已发生在吡嗪环上；描述了其他硝化作用。

  DOI：

  10.1016/0040-4020(77)80028-8

文献信息

• Synthesis and Biological Investigation of Phenothiazine-Based Benzhydroxamic Acids as Selective Histone Deacetylase 6 Inhibitors
  作者：Katharina Vögerl、Nghia Ong、Johanna Senger、Daniel Herp、Karin Schmidtkunz、Martin Marek、Martin Müller、Karin Bartel、Tajith B. Shaik、Nicholas J. Porter、Dina Robaa、David W. Christianson、Christophe Romier、Wolfgang Sippl、Manfred Jung、Franz Bracher

  DOI：10.1021/acs.jmedchem.8b01090

  日期：2019.2.14

  lines. Structure-activity relationship studies revealed that incorporation of a nitrogen atom into the phenothiazine framework results in increased potency and selectivity for HDAC6 (more than 500-fold selectivity relative to the inhibition of HDAC1, HDAC4, and HDAC8), as rationalized by molecular modeling and docking studies. The binding mode was confirmed by co-crystallization of the potent azaphenothiazine

  吩噻嗪系统被确定为有效和选择性组蛋白脱乙酰基酶6（HDAC6）抑制剂的有利封端基团。在这里，我们报告吩噻嗪及其类似物的制备和系统变化，其中吩噻嗪及其类似物含有苯氧肟酸部分作为锌结合基团。我们通过重组HDAC酶分析，通过蛋白质印迹确定细胞中蛋白质的乙酰化水平（微管蛋白与组蛋白乙酰化）以及评估它们对各种癌细胞系的作用，评估了它们选择性抑制HDAC6的能力。构效关系研究表明，将氮原子掺入吩噻嗪骨架中会提高HDAC6的效力和选择性（相对于HDAC1，HDAC4和HDAC8的抑制作用，选择性高500倍以上），通过分子建模和对接研究合理化。通过有效的氮杂吩噻嗪抑制剂与来自Danio rerio HDAC6的催化结构域2的共结晶来确认结合模式。
• 1,4-diaza-phenothiazines
  申请人：Merck Frosst Canada, Inc.

  公开号：US04634766A1

  公开（公告）日：1987-01-06

  Compounds of the Formula I: ##STR1## are inhibitors of the mammalian 5-lipoxygenase enzyme system of the arachidonic acid cascade. As such, these compounds are useful therapeutic agents for treating allergic conditions, asthma, cardiovascular disorders and inflammation.

  公式为I的化合物：##STR1## 是阻止花生四烯酸级联反应中哺乳动物5-脂氧合酶酶系统的抑制剂。因此，这些化合物是治疗过敏症、哮喘、心血管疾病和炎症的有用治疗药物。
• Benzopiperidine derivatives
  申请人：Eisai Co., Ltd.

  公开号：US20040092737A1

  公开（公告）日：2004-05-13

  Benzopiperidine derivatives represented by formula (I), salts thereof or hydrates thereof, processes for producing the same and drugs comprising the same: 1 wherein the variables are as described in the specification. These compounds are useful as drugs efficacious in the prevention and treatment of these various inflammatory diseases and immunologic diseases, such as rheumatoid arthritis, atopic dermatitis, psoriasis, asthma, and rejection reaction accompanying organ transplantation.

  式（I）所表示的苯并哌啶衍生物及其盐或水合物，制备该化合物的方法和包含该化合物的药物：1其中，变量如规范所述。这些化合物在预防和治疗各种炎症性疾病和免疫性疾病方面具有药效，例如类风湿性关节炎、特应性皮炎、银屑病、哮喘和器官移植伴随的排斥反应。
• BENZOPIPERIDINE DERIVATIVES
  申请人：Eisai Co., Ltd.

  公开号：EP0934941A1

  公开（公告）日：1999-08-11

  This invention provides a benzopiperidine derivative represented by the following general formula (I), its salt or hydrates thereof:    wherein R1 to R3 may be the same or different and each represents hydrogen, optionally substituted lower alkyl, optionally substituted lower cycloalkyl or the like, provided that the case where R1 to R3 each represents methyl in the case of lower alkyl is excluded; R represents hydrogen, lower alkyl or the like; E represents N, C or the like; Z represents O, S, SO, SO2 or the like; and the ring G represents an optionally substituted heteroaryl ring having one or more nitrogen atoms. Those are effectively used for a drug for preventing or remedying inflammatory immunologic diseases and autoimmune diseases, or a drug for preventing or remedying rheumatism, collagen disease, asthma, nephritis, ischemic reflow disorders, psoriasis, atopic dermatitis or rejection reaction accompanying organ transplantation.

  本发明提供了由以下通式(I)代表的苯并哌啶衍生物、其盐或水合物： 其中 R1 至 R3 可以相同或不同，各自代表氢、任选取代的低级烷基、任选取代的低级环烷基或类似物，但不包括 R1 至 R3 在低级烷基中各自代表甲基的情况；R 代表氢、低级烷基或类似物；E 代表 N、C 或类似物；Z 代表 O、S、SO、SO2 或类似物；环 G 代表具有一个或多个氮原子的任选取代的杂芳基环。这些药物可有效用于预防或治疗炎症性免疫疾病和自身免疫疾病，或用于预防或治疗风湿病、胶原病、哮喘、肾炎、缺血性回流障碍、牛皮癣、特应性皮炎或器官移植时的排斥反应。
• HETEROCYCLE-FUSED BENZOTHIAZINE DERIVATIVES
  申请人：Eisai Co., Ltd.

  公开号：EP1057830A1

  公开（公告）日：2000-12-06

  The invention provides a novel heterocyclic ring condensed benzothiazine compound which is effective for prevention or remedy of disease, in which histamine, leukotriene and the like participate. The heterocyclic ring condensed benzothiazine compound of the present invention or a pharmacologically acceptable salt thereof is effective for prevention or remedy of disease, in which a chemical mediator, such as histamine, leukotriene and the like, participate, for example, asthma, allergic coryza, atopic dermatitis, hives, hay fever, gastrointestinal allergy, food allergy and the like. Further, the heterocyclic ring condensed benzothiazine compound of the present invention, its pharmacologically acceptable salt or hydrates thereof is represented by the following formula: In the formula, the ring Het represents an unsaturated heterocyclic ring; R1 and R2 are the same as or different from each other, and each represents halogen atom, a lower alkyl group that may be substituted with a halogen atom, a lower alkoxy group that may be substituted with a halogen atom, a lower alkyl lower alkoxy group, cyano group; D represents a lower alkylene group and the like that may have a substituent; Q represents, for example, the formula -NR20R21 (in the formula, R20 and R21 are the same as or different from each other, and each represents hydrogen atom, a lower alkyl group that may be substituted with a halogen atom, an aryl group that may have a substituent, an arylalkyl group that may have a substituent, a heteroaryl group that may have a substituent or a heteroarylalkyl group that may have a substituent, or R20 and R21 may form a 3- to 8-membered ring along with the nitrogen atom to which they are bound); and x represents an integer of from 1 to 2.

  本发明提供了一种新型杂环缩合苯并噻嗪化合物，可有效预防或治疗组胺、白三烯等参与的疾病。本发明的杂环缩合苯并噻嗪化合物或其药理学上可接受的盐可有效预防或治疗化学介质（如组胺、白三烯等）参与的疾病，如哮喘、过敏性苍白喉、特应性皮炎、荨麻疹、花粉症、胃肠道过敏、食物过敏等。此外，本发明的杂环缩合苯并噻嗪化合物、其药理学上可接受的盐或其水合物由下式表示： 式中，环 Het 代表不饱和杂环；R1 和 R2 彼此相同或不同，各自代表卤原子、可被卤原子取代的低级烷基、可被卤原子取代的低级烷氧基、低级烷基低级烷氧基、氰基；D 代表可具有取代基的低级亚烷基等；Q 代表例如式-NR20R21（式中，R20 和 R21 彼此相同或不同，且各自代表氢原子、可被卤素原子取代的低级烷基、可具有取代基的芳基、可具有取代基的芳烷基、可具有取代基的杂芳基或可具有取代基的杂芳基烷基，或 R20 和 R21 可与它们结合的氮原子一起形成 3 至 8 元环）；x 代表 1 至 2 的整数。