3-N,3-N,7-N,7-N,1,9-hexamethyl-10H-phenothiazine-3,7-diamine

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噻嗪类
• 英文名称: 3-N,3-N,7-N,7-N,1,9-hexamethyl-10H-phenothiazine-3,7-diamine
• 化学式: C₁₈H₂₃N₃S
• 分子量: 313.5
• InChiKey: XSAUZIURVGEXFA-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  22
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  43.8
• 氢给体数：
  1
• 氢受体数：
  4

文献信息

• 3,7-DIAMINO-10H-PHENOTHIAZINE SALTS AND THEIR USE
  申请人：Wischik Claude Michel

  公开号：US20090054419A1

  公开（公告）日：2009-02-26

  This invention pertains generally to the field of phenothiazine compounds, and more particularly to certain stably reduced phenothiazine compounds, specifically, certain 3,7 diamino-10H-phenothiazine (DAPTZ) compounds of the following formula wherein: each of R 1 and R 9 is independently selected from: —H; C 1-4 alkyl; C 2-4 alkenyl; and halogenated C 1-4 alkyl; each of R 3NA and R 3NB is independently selected from: —H; C 1-4 alkyl; C 2-4 alkenyl; and halogenated C 1-4 alkyl; each of R 7NA and R 7NB is independently selected from: —H; C 1-4 alkyl; C 2-4 alkenyl; and halogenated C 1-4 alkyl; each of HX 1 and HX 2 is independently a protic acid; and pharmaceutically acceptable salts, solvates, and hydrates thereof. These compounds are useful as drugs, for example, in the treatment of tauopathies, such as Alzheimer's disease, and also as prodrugs for the corresponding oxidized thioninium drugs (for example, methythioninium chloride, MTC).

  本发明涉及苯并噻嗪化合物领域，更具体地涉及某些稳定还原的苯并噻嗪化合物，具体而言，涉及以下式子的某些3,7-二氨基-10H-苯并噻嗪(DAPTZ)化合物：其中：R1和R9各自独立地选自：—H；C1-4烷基；C2-4烯基；和卤代C1-4烷基；R3NA和R3NB各自独立地选自：—H；C1-4烷基；C2-4烯基；和卤代C1-4烷基；R7NA和R7NB各自独立地选自：—H；C1-4烷基；C2-4烯基；和卤代C1-4烷基；HX1和HX2各自独立地为质子酸；以及其药学上可接受的盐、溶剂化合物和水合物。这些化合物在药物方面具有用途，例如在治疗tau蛋白病中，如阿尔茨海默病，并且作为相应氧化噻唑铵药物（例如甲基噻唑铵盐，MTC）的前药。
• 3,7-DIAMINO-10H-PHINOTHIAZINE SALTS AND THEIR USE
  申请人：WISCHIK Claude Michel

  公开号：US20110118242A1

  公开（公告）日：2011-05-19

  This invention pertains generally to the field of phenothiazine compounds, and more particularly to certain stably reduced phenothiazine compounds, specifically, certain 3,7-diamino-10H-phenothiazine (DAPTZ) compounds of the following formula: wherein: each of R 1 and R 9 is independently selected from: —H; C 1-4 alkyl; C 2-4 alkenyl; and halogenated C 1-4 alkyl; each of R 3NA and R 3NB is independently selected from: —H; C 1-4 alkyl; C 2-4 alkenyl; and halogenated C 1-4 alkyl; each of R 7NA and R 7NB is independently selected from: —H; C 1-4 alkyl; C 2-4 alkenyl; and halogenated C 1-4 alkyl; each of HX 1 and HX 2 is independently a protic acid; and pharmaceutically acceptable salts, solvates, and hydrates thereof. These compounds are useful as drugs, for example, in the treatment of tauopathies, such as Alzheimer's disease, and also as prodrugs for the corresponding oxidized thioninium drugs (for example, methylthioninium chloride, MTC).

  本发明涉及苯并噻嗪化合物领域，更具体地涉及某些稳定还原的苯并噻嗪化合物，具体而言，涉及以下式子的某些3,7-二氨基-10H-苯并噻嗪（DAPTZ）化合物： 其中：R1和R9各自独立地选择自：—H；C1-4烷基；C2-4烯基；和卤代的C1-4烷基；R3NA和R3NB各自独立地选择自：—H；C1-4烷基；C2-4烯基；和卤代的C1-4烷基；R7NA和R7NB各自独立地选择自：—H；C1-4烷基；C2-4烯基；和卤代的C1-4烷基；HX1和HX2各自独立地是质子酸；以及其药学上可接受的盐、溶剂化合物和水合物。这些化合物可用作药物，例如，用于治疗tau蛋白病，如阿尔茨海默病，并且还可作为相应氧化硫鎓药物（例如甲基硫鎓盐酸盐，MTC）的前药。
• COMPOUNDS, COMPOSITIONS, AND METHODS FOR TREATING ALZHEIMER'S DISEASE
  申请人：Prosetta Antiviral Inc.

  公开号：US20140315897A1

  公开（公告）日：2014-10-23

  Novel methods and compounds for treating Alzheimer's Disease are provided. In one aspect, the invention provides methods for treating Alzheimer's Disease by administering certain phenothiazine derivatives. In one embodiment, the methods include administering an effective amount of a 3-oxo-7-dialkyl-amino-phenothiazine derivative, or 3-oxo-7-dialkyl-amino-phenothiazine. In another embodiment, the invention provides methods for treating Alzheimer's Disease by administering an effective amount of a 3,7-diazetidin-1-yl-phenothiazine or a derivative thereof. In another aspect, the invention provides novel azetidinyl phenothiazine compounds.

  本发明提供了治疗阿尔茨海默病的新方法和化合物。在一个方面，本发明提供了通过给予某些苯并噻嗪衍生物治疗阿尔茨海默病的方法。在一个实施例中，该方法包括给予有效量的3-氧代-7-二烷基氨基苯并噻嗪衍生物或3-氧代-7-二烷基氨基苯并噻嗪。在另一个实施例中，本发明提供了通过给予有效量的3,7-二氮杂-1-基苯并噻嗪或其衍生物治疗阿尔茨海默病的方法。在另一个方面，本发明提供了新的氮杂环苯并噻嗪化合物。
• 3, 7-DIAMINO-10H-PHENOTHIAZINE SALTS AND THEIR USE
  申请人：WisTa Laboratories Ltd.

  公开号：US20160051559A1

  公开（公告）日：2016-02-25

  Described are methods of preparing reduced 3,7-diamino-10H-phenothiazine (DAPTZ) compounds of formula: wherein: R 1 and R 9 are independently selected from: —H; C 1-4 alkyl; C 2-4 alkenyl; and halogenated C 1-4 alkyl; each of R 3NA and R 3NB is independently selected from: —H; C 1-4 alkyl; C 2-4 alkenyl; and halogenated C 1-4 alkyl; each of R 7NA and R 7NB is independently selected from: —H; C 1-4 alkyl; C 2-4 alkenyl; and halogenated C 1-4 alkyl; each of HX 1 and HX 2 is independently a protic acid; and pharmaceutically acceptable salts, solvates, and hydrates thereof. These methods are particularly useful for producing stable reduced forms, and with high purity. The stability and purity are especially relevant for pharmaceutical compositions for the treatment of disease. The compounds are useful for treatment of e.g. tauopathies, such as Alzheimer's disease, and also as prodrugs for the corresponding oxidized thioninium drugs.

  本文描述了制备式为的还原型3,7-二氨基-10H-苯并噻嗪（DAPTZ）化合物的方法：其中：R1和R9分别独立地选择自：—H；C1-4烷基；C2-4烯基；和卤代C1-4烷基；R3NA和R3NB中的每个都是独立地选择自：—H；C1-4烷基；C2-4烯基；和卤代C1-4烷基；R7NA和R7NB中的每个都是独立地选择自：—H；C1-4烷基；C2-4烯基；和卤代C1-4烷基；HX1和HX2中的每个都是独立的质子酸；以及其药学上可接受的盐、溶剂化合物和水合物。这些方法特别适用于生产稳定的还原型，且纯度高。稳定性和纯度对于治疗疾病的制药组合物尤为重要。该化合物可用于治疗tau病理学，例如阿尔茨海默病，也可作为相应氧化噻唑啉药物的前药。
• METHOD FOR DETECTION OF PHENOTHIAZINE DERIVATIVE DYE, AND COLOR-DEVELOPER REAGENT FOR USE IN THE METHOD
  申请人：Arkray, Inc.

  公开号：EP2108952A1

  公开（公告）日：2009-10-14

  The present invention provides a phenothiazine-derivative color-measuring method that can detect a phenothiazine-derivative color even at a wavelength longer than the wavelength that exhibits maximum absorption. A phenothiazine-derivative color is detected, by adding a 5-hydroxy-1-(4-sulfophenyl)-4-(4-sulfophenylazo)pyrazole-3-carboxylic acid salt, 6-hydroxy-5-(4-sulfophenylazo)-2-naphthalenesulfonic acid salt, 3-hydroxy-4-(4-sulfonaphthylazo)-2,7-naphthalenedisulfonic acid salt, 7-hydroxy-8-(4-sulfonaphthylazo)-1,3-naphthalenedisulfonic acid salt, 3',6'-dihydroxy-2',4',5',7'-tetraiodospiro[isobenzofuran-1(3H),9'-(9H) xanthene]-3-one salt, 3',6'-dihydroxy-2',4',5',7'-tetrabromo-4,5,6,7,-tetrachlorospiro[isobenzofuran-1( 3H),9'-[9H] xanthene]-3-one salt, 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5',7'-tetraiodospiro[isobenzofuran-1(3H ),9'-[9H] xanthene]-3-one salt or flavonoid-based color to the reaction system containing a phenothiazine-derivative color, and then measuring the light absorbance at a wavelength of 610 to 730 nm.

  本发明提供了一种吩噻嗪衍生物颜色测量方法，它甚至可以在比显示最大吸收的波长更长的波长上检测吩噻嗪衍生物颜色。通过加入 5-羟基-1-(4-磺酸苯基)-4-(4-磺酸苯基偶氮)吡唑-3-羧酸盐、6-羟基-5-(4-磺酸苯基偶氮)-2-萘磺酸盐，可检测出吩噻嗪衍生物颜色、3-羟基-4-(4-磺酸基萘偶氮)-2,7-萘二磺酸盐，7-羟基-8-(4-磺酸基萘偶氮)-1,3-萘二磺酸盐，3',6'-二羟基-2',4',5',7'-四碘螺[异苯并呋喃-1(3H)、9'-(9H)氧杂蒽]-3-酮盐、3',6'-二羟基-2',4',5',7'-四溴-4,5,6,7,-四氯螺[异苯并呋喃-1(3H)、9'-[9H] xanthene]-3-one salt, 4,5,6,7-tetrachloro-3',6'-dihydroxy-2',4',5',7'-tetraiodospiro[isobenzofuran-1(3H )、在含有吩噻嗪衍生物色素的反应体系中加入 9'-[9H]氧杂蒽]-3-酮盐或黄酮类色素，然后测量波长为 610 至 730 纳米的吸光度。