1,9-dimethyl methylene blue | 71481-78-2

• 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: 1,9-dimethyl methylene blue
• 英文别名: Phenothiazin-5-ium, 3,7-bis(dimethylamino)-1,9-dimethyl-；[7-(dimethylamino)-1,9-dimethylphenothiazin-3-ylidene]-dimethylazanium
• CAS: 71481-78-2
• 化学式: C₁₈H₂₂N₃S
• 分子量: 312.459
• InChiKey: VVEWWLHKADXQQL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  22
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  43.9
• 氢给体数：
  0
• 氢受体数：
  3

文献信息

• METHODS OF SYNTHESIS AND/OR PURIFICATION OF DIAMINOPHENOTHIAZINIUM COMPOUNDS
  申请人：WisTa Laboratories Ltd.

  公开号：US20160296531A1

  公开（公告）日：2016-10-13

  Disclosed are methods of synthesis and/or purification of certain 3,7-diamino-phenothiazin-5-ium compounds (“diaminophenothiazinium compounds”) including Methylthioninium Chloride (MTC) (Methylene Blue), and the resulting high purity characterized by a purity greater than 98%, and very low levels of heavy metals and organic impurities Azure A, B, C and MVB. Also disclosed are methods of treatment of a tauopathy or methemoglobinemia in a patient in need thereof, comprising administering to the patient a therapeutically effective amount of the high-purity diaminophenothiazinium compound.

  本发明涉及一种合成和/或纯化某些3,7-二氨基苯并噻吩-5-ium化合物（“二氨基苯并噻吩-5-ium化合物”）的方法，包括氯甲亚绿（亚甲蓝）的甲硫氧化物（Methylthioninium Chloride，MTC），并且所得到的高纯度具有大于98％的纯度，并且重金属和有机杂质Azure A、B、C和MVB的水平非常低。本发明还涉及一种治疗需要治疗tau病理或高铁血红蛋白血症的患者的方法，包括向患者施用治疗有效量的高纯度二氨基苯并噻吩-5-ium化合物。
• METHODS OF CHEMICAL SYNTHESIS AND PURIFICATION OF DIAMINOPHENOTHIAZINIUM COMPOUNDS INCLUDING METHYLTHIONINIUM CHLORIDE (MTC)
  申请人：STOREY John Mervyn David

  公开号：US20110021510A1

  公开（公告）日：2011-01-27

  This invention pertains generally to the field of chemical synthesis and purification, and more specifically to methods of synthesizing and purifying certain 3,7 diamino-phenothiazin-5-ium compounds (referred to herein as “diaminophenothiaziniumcompounds”) including Methylhioninium Chloride (MTC) (also known as Methylene Blue). In one embodiment, the method comprises the steps of, in order: nitrosylation (NOS); nitrosyl reduction (NR); thiosulfonic acid formation (TSAF); oxidative coupling (OC); Cr(VI) reduction (CR); isolation and purification of zwitterionic intermediate (IAPOZI); ring closure (RC); chloride salt-formation (CSF); one of: sulphide treatment (ST); dimethyldithiocarbamate treatment (DT); carbonate treatment (CT); ethylenediaminetetraacetic acid treatment (EDTAT); organic extraction (OE); and recrystallisation (RX). The present invention also pertains to the resulting (high purity) compounds, compositions comprising them (e.g., tablets, capsules), and their use in methods of inactivating pathogens, and methods of medical treatment and diagnosis, etc., for example, for tauopathies, Alzheimer's disease (AD), skin cancer, melanoma, viral diseases, bacterial diseases, or protozoal diseases.

  本发明一般涉及化学合成和纯化领域，更具体地涉及合成和纯化某些3,7-二氨基苯并噻吩-5-ium化合物（以下简称“二氨基苯并噻吩-5-ium化合物”），包括氯化甲基亚啶（MTC）（也称亚甲蓝）。在一种实施例中，该方法包括以下步骤：亚硝基化（NOS）；亚硝基还原（NR）；硫代磺酸形成（TSAF）；氧化偶联（OC）；Cr（VI）还原（CR）；离子交换分离和纯化中间产物（IAPOZI）；环合成（RC）；氯化物盐形成（CSF）；其中之一：硫化物处理（ST）；二甲基二硫代氨基甲酸盐处理（DT）；碳酸盐处理（CT）；乙二胺四乙酸处理（EDTAT）；有机萃取（OE）；和再结晶（RX）。本发明还涉及所得（高纯度）化合物、包含它们的组合物（例如，片剂、胶囊）以及它们在灭活病原体、医疗治疗和诊断等方面的使用方法，例如用于tau病变、阿尔茨海默病（AD）、皮肤癌、黑色素瘤、病毒性疾病、细菌性疾病或原虫性疾病。
• HIGH PURITY DIAMINOPHENOTHIAZINIUM COMPOUNDS INCLUDING METHYLTHIONINIUM CHLORIDE (MTC)
  申请人：WisTa Laboratories Ltd.

  公开号：US20160129009A1

  公开（公告）日：2016-05-12

  This invention pertains generally to the field of chemical synthesis and purification, and more specifically to methods of synthesizing and purifying certain 3,7 diamino-phenothiazin-5-ium compounds (referred to herein as “diaminophenothiaziniumcompounds”) including Methythioninium Chloride (MTC) (also known as Methylene Blue). In one embodiment, the method comprises the steps of, in order: nitrosylation (NOS); nitrosyl reduction (NR); thiosulfonic acid formation (TSAF); oxidative coupling (OC); Cr(VI) reduction (CR); isolation and purification of zwitterionic intermediate (IAPOZI); ring closure (RC); chloride salt-formation (CSF); one of: sulphide treatment (ST); dimethyldithiocarbamate treatment (DT); carbonate treatment (CT); ethylenediaminetetraacetic acid treatment (EDTAT); organic extraction (OE); and recrystallisation (RX). The present invention also pertains to the resulting (high purity) compounds, compositions comprising them (e.g., tablets, capsules), and their use in methods of inactivating pathogens, and methods of medical treatment and diagnosis, etc., for example, for tauopathies, Alzheimer's disease (AD), skin cancer, melanoma, viral diseases, bacterial diseases, or protozoal diseases.

  本发明涉及化学合成和纯化领域，更具体地涉及合成和纯化某些3,7-二氨基苯并噻嗪-5-ium化合物（以下简称“二氨基苯并噻嗪化合物”），包括氯化甲亚硫胺（MTC）（也称为亚甲蓝）。在一种实施例中，该方法依次包括以下步骤：亚硝基化（NOS）；亚硝基还原（NR）；硫代磺酸形成（TSAF）；氧化偶联（OC）；Cr（VI）还原（CR）；离子对中间体的分离和纯化（IAPOZI）；环闭合（RC）；氯化物盐形成（CSF）；其中之一：硫化物处理（ST）；二甲基二硫代氨基甲酸盐处理（DT）；碳酸盐处理（CT）；乙二胺四乙酸处理（EDTAT）；有机萃取（OE）；和再结晶（RX）。本发明还涉及所得到的（高纯度）化合物，包括它们的组合物（例如，片剂、胶囊），以及它们在灭活病原体、医疗治疗和诊断等方面的应用，例如用于tau病理、阿尔茨海默病（AD）、皮肤癌、黑色素瘤、病毒疾病、细菌疾病或原虫疾病。
• Methods of chemical synthesis and purification of diaminophenothiazinium compounds including methylthioninium chloride (MTC)
  申请人：WisTa Laboratories Ltd.

  公开号：US20170209456A1

  公开（公告）日：2017-07-27

  This disclosure pertains generally to the field of chemical synthesis and purification, and more specifically to methods of synthesizing and purifying certain 3,7 diamino-phenothiazin-5-ium compounds (referred to herein as “diaminophenothiaziniumcompounds”) including Methythioninium Chloride (MTC) (also known as Methylene Blue). In one embodiment, the method comprises the steps of, in order: nitrosylation (NOS); nitrosyl reduction (NR); thiosulfonic acid formation (TSAF); oxidative coupling (OC); Cr(VI) reduction (CR); isolation and purification of zwitterionic intermediate (IAPOZI); ring closure (RC); chloride salt-formation (CSF); one of: sulphide treatment (ST); dimethyldithiocarbamate treatment (DT); carbonate treatment (CT); ethylenediaminetetraacetic acid treatment (EDTAT); organic extraction (OE); and recrystallisation (RX). Also disclosed resulting (high purity) compounds, compositions comprising them (e.g., tablets, capsules), and their use in methods of inactivating pathogens, and methods of medical treatment and diagnosis, etc., for example, for tauopathies, Alzheimer's disease (AD), skin cancer, melanoma, viral diseases, bacterial diseases, or protozoal diseases.

  本公开涉及化学合成和纯化领域，更具体地涉及合成和纯化某些3,7-二氨基苯并噻吩-5-铵化合物（以下简称“二氨基苯并噻吩铵化合物”），包括氯化甲亚硫基苯并噻吩（MTC）（也称为亚甲蓝）的合成方法。在一种实施例中，该方法依次包括以下步骤：硝基化（NOS）；硝基还原（NR）；硫代磺酸形成（TSAF）；氧化偶联（OC）；Cr（VI）还原（CR）；离子对中间体的分离和纯化（IAPOZI）；环闭合（RC）；氯化物盐形成（CSF）；其中之一：硫化物处理（ST）；二甲基二硫代氨基甲酸盐处理（DT）；碳酸盐处理（CT）；乙二胺四乙酸处理（EDTAT）；有机萃取（OE）；和再结晶（RX）。还公开了由此得到的（高纯度）化合物，包括它们的组合物（例如，片剂、胶囊），以及它们在灭活病原体、医疗治疗和诊断等方面的用途，例如用于tau病理、阿尔茨海默病（AD）、皮肤癌、黑色素瘤、病毒性疾病、细菌性疾病或原虫性疾病。
• Methods of Chemical Synthesis and Purification of Diaminophenothiazinium Compounds Including Methylthioninium Chloride (Mtc)
  申请人：Storey John Mervyn David

  公开号：US20080207603A1

  公开（公告）日：2008-08-28

  This invention pertains generally to the field of chemical synthesis and purification, and more specifically to methods of synthesizing and purifying certain 3,7 diamino-phenothiazin-5-ium compounds (referred to herein as “diaminophenothiazinium compounds”) including Methylthioninium Chloride (MTC) (also known as Methylene Blue). In one embodiment, the method comprises the steps of, in order: nitrosylation (NOS); nitrosyl reduction (NR); thiosulfonic acid formation (TSAF); oxidative coupling (OC); Cr(VI) reduction (CR); isolation and purification of zwitterionic intermediate (IAPOZI); ring closure (RC); chloride salt formation (CSF); one of: sulphide treatment (ST); dimethyldithiocarbamate treatment (DT); carbonate treatment (CT); ethylenediaminetetraacetic acid treatment (EDTAT); organic extraction (OE); and recrystallisation (RX). The present invention also pertains to the resulting (high purity) compounds, compositions comprising them (e.g., tablets, capsules), and their use in methods of inactivating pathogens, and methods of medical treatment and diagnosis, etc., for example, for tauopathies, Alzheimer's disease (AD), skin cancer, melanoma, viral diseases, bacterial diseases, or protozoal diseases. Wherein: each of R 1 and R 9 is independently selected from: —H; C 1-4 alkenyl; and halogenated C 1-4 alkyl; each of R 3NA and R 3NB is independently selected from: C 1-4 alkyl; C 2-4 alkenyl; and halogenated C 4-1 alkyl; each of R 7NA and R 7NB is independently selected from: C 1-4 alkyl; C 2-4 alkenyl; and halogenated C 1-4 alkyl; and X is one or more anionic counter ions to achieve electrical neutrality.

  本发明涉及化学合成和纯化领域，更具体地涉及合成和纯化某些3,7-二氨基苯并噻吩-5-ium化合物（以下简称“二氨基苯并噻吩化合物”），包括氯甲亚蓝（MTC）（也称为亚甲蓝）的方法。在一种实施例中，该方法依次包括以下步骤：亚硝基化（NOS）；亚硝基还原（NR）；硫代磺酸酯形成（TSAF）；氧化偶合（OC）；Cr（VI）还原（CR）；离子对中间体的分离和纯化（IAPOZI）；环闭合（RC）；氯化物盐形成（CSF）；其中之一：硫化物处理（ST）；二甲基二硫脲处理（DT）；碳酸盐处理（CT）；乙二胺四乙酸处理（EDTAT）；有机萃取（OE）；和再结晶（RX）。本发明还涉及所得到的（高纯度）化合物，包括它们的组合物（例如，片剂，胶囊），以及它们在灭活病原体，医疗治疗和诊断等方法中的使用，例如，用于tau病理，阿尔茨海默病（AD），皮肤癌，黑色素瘤，病毒性疾病，细菌性疾病或原虫性疾病。其中：R1和R9各自独立地选自：—H；C1-4烯基；和卤代C1-4烷基；R3NA和R3NB各自独立地选自：C1-4烷基；C2-4烯基；和卤代C4-1烷基；R7NA和R7NB各自独立地选自：C1-4烷基；C2-4烯基；和卤代C1-4烷基；X是一个或多个阴离子对以达到电中性。