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    High purity diaminophenothiazinium compounds including methylthioninium chloride (MTC)
    1.
    发明授权
    High purity diaminophenothiazinium compounds including methylthioninium chloride (MTC) 有权
    高纯度二氨基吩噻嗪鎓化合物，包括甲基硫堇（MTC）

    公开(公告)号：US09242946B2

    公开(公告)日：2016-01-26

    申请号：US12875465

    申请日：2010-09-03

    申请人： John Mervyn David Storey ,  James Peter Sinclair ,  Colin Marshall ,  Han Wan Tan ,  Claude Michel Wischik

    发明人： John Mervyn David Storey ,  James Peter Sinclair ,  Colin Marshall ,  Han Wan Tan ,  Claude Michel Wischik

    IPC分类号： C07D279/18 ,  C09B19/02

    CPC分类号： A61K31/5415 ,  A61K9/0019 ,  A61K49/006 ,  C07D279/18 ,  C09B19/02 ,  G01N33/52 ,  Y02A50/393

    摘要： 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.

    摘要翻译： 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 - 吩噻嗪-5-鎓化合物（本文称为“二氨基吩噻嗪鎓化合物”）的方法，包括甲基氯化铑（MTC）（ 也称为亚甲基蓝）。 在一个实施方案中，该方法包括以下步骤：按顺序：亚硝基化（NOS）; 亚硝酰还原（NR）; 硫代磺酸形成（TSAF）; 氧化偶合（OC）; Cr（VI）还原（CR）; 两性离子中间体（IAPOZI）的分离和纯化; 闭环（RC）; 氯化物盐形成（CSF）; 一种：硫化物处理（ST）; 二甲基二硫代氨基甲酸酯处理（DT）; 碳酸盐处理（CT）; 乙二胺四乙酸处理（EDTAT）; 有机萃取（OE）; 和重结晶（RX）。 本发明还涉及所得的（高纯度）化合物，包含它们的组合物（例如片剂，胶囊）及其在灭活病原体的方法中的用途，以及治疗和诊断方法等，例如对于tau蛋白病 ，阿尔茨海默病（AD），皮肤癌，黑素瘤，病毒性疾病，细菌性疾病或原生动物疾病。

    METHODS OF CHEMICAL SYNTHESIS AND PURIFICATION OF DIAMINOPHENOTHIAZINIUM COMPOUNDS INCLUDING METHYLTHIONINIUM CHLORIDE (MTC)
    4.
    发明申请
    METHODS OF CHEMICAL SYNTHESIS AND PURIFICATION OF DIAMINOPHENOTHIAZINIUM COMPOUNDS INCLUDING METHYLTHIONINIUM CHLORIDE (MTC) 有权
    化学合成和纯化包括氯化亚甲基氯化铵（MTC）的二氨基苯甲酸盐化合物的方法

    公开(公告)号：US20110021510A1

    公开(公告)日：2011-01-27

    申请号：US12875465

    申请日：2010-09-03

    申请人： John Mervyn David STOREY ,  James Peter SINCLAIR ,  Colin MARSHALL ,  Han Wan TAN ,  Claude Michel WISCHIK

    发明人： John Mervyn David STOREY ,  James Peter SINCLAIR ,  Colin MARSHALL ,  Han Wan TAN ,  Claude Michel WISCHIK

    IPC分类号： A61K31/5415 ,  C07D279/20 ,  A01N43/84 ,  A61P31/12 ,  A61P33/02 ,  A61P35/00 ,  A61P31/14 ,  A61P31/18 ,  A61P25/28 ,  A61P31/04

    CPC分类号： A61K31/5415 ,  A61K9/0019 ,  A61K49/006 ,  C07D279/18 ,  C09B19/02 ,  G01N33/52 ,  Y02A50/393

    摘要： 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.

    摘要翻译： 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 - 吩噻嗪-5-鎓化合物（本文称为“二氨基吩噻嗪鎓化合物”）的方法，包括甲基氯化铑（MTC）（ 也称为亚甲基蓝）。 在一个实施方案中，该方法包括以下步骤：按顺序：亚硝基化（NOS）; 亚硝酰还原（NR）; 硫代磺酸形成（TSAF）; 氧化偶合（OC）; Cr（VI）还原（CR）; 两性离子中间体（IAPOZI）的分离和纯化; 闭环（RC）; 氯化物盐形成（CSF）; 一种：硫化物处理（ST）; 二甲基二硫代氨基甲酸酯处理（DT）; 碳酸盐处理（CT）; 乙二胺四乙酸处理（EDTAT）; 有机萃取（OE）; 和重结晶（RX）。 本发明还涉及所得的（高纯度）化合物，包含它们的组合物（例如片剂，胶囊）及其在灭活病原体的方法中的用途，以及治疗和诊断方法等，例如对于tau蛋白病 ，阿尔茨海默病（AD），皮肤癌，黑素瘤，病毒性疾病，细菌性疾病或原生动物疾病。

    Methods of chemical synthesis of diaminophenothiazinium compounds involving the use of persulfate oxidants
    10.
    发明授权
    Methods of chemical synthesis of diaminophenothiazinium compounds involving the use of persulfate oxidants 有权
    涉及使用过硫酸盐氧化剂的二氨基吩噻嗪鎓化合物的化学合成方法

    公开(公告)号：US08691979B2

    公开(公告)日：2014-04-08

    申请号：US13318907

    申请日：2010-05-11

    申请人： Christopher Paul Larch ,  John Mervyn David Storey ,  Craig Williamson ,  Colin Marshall ,  Steven John Kemp

    发明人： Christopher Paul Larch ,  John Mervyn David Storey ,  Craig Williamson ,  Colin Marshall ,  Steven John Kemp

    IPC分类号： C07D279/18 ,  A61K31/5415

    CPC分类号： C07D279/18 ,  C07C381/02

    摘要： Described are methods of synthesizing and purifying certain 3,7-diamino-phenothiazin-5-ium compounds (referred to herein as “diaminophenothiazinium compounds”) including Methylhioninium Chloride (MTC) (also known as Methylene Blue). In one embodiment, the method comprises the steps of, in order: a thiosulfonic acid formation (TSAF); an oxidative coupling (OC); and a ring closure (RC). Also described are resulting compounds and compositions comprising them (e.g., tablets, capsules) for use in methods of medical treatment and diagnosis, etc., for example, for tauopathies, or Alzheimer's disease (AD).

    摘要翻译： 描述了合成和纯化包括甲基硫堇（MTC）（也称为亚甲基蓝）的某些3,7-二氨基吩噻嗪-5-肟化合物（本文称为“二氨基吩噻嗪鎓化合物”）的方法。 在一个实施方案中，该方法包括以下步骤：顺序：硫代磺酸形成（TSAF）; 氧化偶联（OC）; 和闭环（RC）。 还描述了用于医学治疗和诊断方法等的例如用于tau蛋白病或阿尔茨海默氏病（AD）的所得化合物和包含它们的组合物（例如片剂，胶囊）。