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1. 发明申请

WO2007110627A3 3,7-DIAMINO-10H-PHENOTHIAZINE SALTS AND THEIR USE 审中-公开
标题翻译： 3,7-二氨基-10H-苯并恶嗪盐及其用途
公开(公告)号：WO2007110627A3
公开(公告)日：2007-11-22
申请号：PCT/GB2007001103
申请日：2007-03-28
申请人： WISTA LAB LTD , WISCHIK CLAUDE MICHEL , RICKARD JANET ELIZABETH , HARRINGTON CHARLES ROBERT , HORSLEY DAVID , STOREY JOHN MERVYN DAVID , MARSHALL COLIN , SINCLAIR JAMES PETER , BADDELEY THOMAS CRAVEN
发明人： WISCHIK CLAUDE MICHEL , RICKARD JANET ELIZABETH , HARRINGTON CHARLES ROBERT , HORSLEY DAVID , STOREY JOHN MERVYN DAVID , MARSHALL COLIN , SINCLAIR JAMES PETER , BADDELEY THOMAS CRAVEN
IPC分类号： C07D279/20 , A61K31/5415 , A61P25/28
CPC分类号： A61K31/5415 , C07D279/20 , C07D279/22 , C09B21/00
摘要： 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).
摘要翻译：本发明一般涉及吩噻嗪化合物领域，更具体地涉及某些稳定还原的吩噻嗪化合物，特别是下式的某些3,7-二氨基-10H-吩噻嗪（DAPTZ）化合物，其中：每个R 1，其中R 9和R 9独立地选自：-H; ç_{1-4 烷基; ç_{2-4 烯基; 和卤代C 1-4烷基; R 3NA和R 3NB中的每一个独立地选自：-H; ç_{1-4 烷基; ç_{2-4 烯基; 和卤代C 1-4烷基; R 7NA和R 7NB中的每一个独立地选自：-H; ç_{1-4 烷基; ç_{2-4 烯基; 和卤代C 1-4烷基; HX 1和HX 2各自独立地为质子酸; 及其药学上可接受的盐，溶剂化物和水合物。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氏病，以及还用作相应的氧化th drugs类药物（例如甲硫in氯化物，MTC）的前体药物。}}}}}}

2. 发明申请

WO2008007074A3 METHODS OF SYNTHESIS AND/OR PURIFICATION OF DIAMINOPHENOTHIAZINIUM COMPOUNDS 审中-公开
标题翻译：二氨基苯并噻唑鎓化合物的合成和/或纯化方法
公开(公告)号：WO2008007074A3
公开(公告)日：2008-02-28
申请号：PCT/GB2007002570
申请日：2007-07-10
申请人： WISTA LAB LTD , WISCHIK CLAUDE MICHEL , STOREY JOHN MERVYN DAVID , MARSHALL COLIN , SINCLAIR JAMES PETER , BADDELEY THOMAS CRAVEN
发明人： WISCHIK CLAUDE MICHEL , STOREY JOHN MERVYN DAVID , MARSHALL COLIN , SINCLAIR JAMES PETER , BADDELEY THOMAS CRAVEN
IPC分类号： C07D279/18
CPC分类号： A61K31/5415 , C07D279/18 , C07D279/20
摘要： This invention pertains generally to the field of chemical synthesis and purification, and more specifically to methods of synthesis and/or purification of certain 3,7 diamino-phenothiazin-5-ium compounds (referred to herein as "diaminophenothiazinium compounds") including Methylthioninium Chloride (MTC) (also known as Methylene Blue). 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, prophylaxis, and diagnosis, etc., for example, a tauopathy; a disease of tau protein aggregation; Alzheimer's disease (AD); Pick's disease; Progressive Supranuclear Palsy (PSP); fronto temporal dementia (FTD); parkinsonism linked to chromosome 17 (FTDP-17); disinhibition-dementia-parkinsonism-amyotrophy complex (DDPAC); pallido-ponto-nigral degeneration (PPND); Guam-ALS syndrome; pallido-nigro-luysian degeneration (PNLD); cortico-basal degeneration (CBD); mild cognitive impairment (MCI); skin cancer; melanoma; methemoglobinemia; a viral infection; a bacterial infection; a protozoal infection; a parasitic infection; malaria; visceral leishmaniasis; African sleeping sickness; toxoplasmosis; giardiasis; Chagas' disease; Hepatitis C virus (HCV) infection; human immunodeficiency virus (HIV) infection; West Nile virus (WNV) infection; a synucleinopathy; Parkinson's disease (PD); dementia with Lewy bodies (DLB); multiple system atrophy (MSA); drug-induced parkinsonism; and pure autonomic failure (PAF).
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”）的合成和/或纯化方法，包括甲基硫堇鎓氯化物（MTC）（也称为亚甲蓝）。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的方法中的用途，以及医学治疗，预防和诊断等的方法，一种tau蛋白病; τ蛋白质聚集的疾病; 阿尔茨海默病（AD）; 皮克氏病; 进行性核上性麻痹（PSP）; 额颞叶痴呆（FTD）; 与17号染色体相关的帕金森综合征（FTDP-17）; 去抑制 - 痴呆 - 帕金森病 - 肌萎缩综合征（DDPAC）; 苍白球 - 黑质变性（PPND）; 关岛 - ALS综合征; pallido-nigro-luysian degeneration（PNLD）; 皮质基底变性（CBD）; 轻度认知障碍（MCI）; 皮肤癌; 黑色素瘤; 高铁血红蛋白血症; 病毒感染; 细菌感染; 原虫感染; 寄生虫感染; 疟疾; 内脏利什曼病; 非洲昏睡病; 弓形虫病; 贾第虫病; 南美锥虫病; 丙型肝炎病毒（HCV）感染; 人类免疫缺陷病毒（HIV）感染; 西尼罗河病毒（WNV）感染; 突触核蛋白病; 帕金森病（PD）; 路易体痴呆（DLB）; 多系统萎缩（MSA）; 药物性帕金森综合征; 和纯自主神经衰竭（PAF）。

3. 发明申请

WO2012107706A8 PHENOTHIAZINE DIAMINIUM SALTS AND THEIR USE 审中-公开
标题翻译：双酚钠金属盐及其使用
公开(公告)号：WO2012107706A8
公开(公告)日：2013-09-19
申请号：PCT/GB2011001221
申请日：2011-08-15
申请人： WISTA LAB LTD , MARSHALL COLIN , CLUNAS SCOTT , STOREY JOHN MERVYN DAVID , SINCLAIR JAMES PETER , BADDELEY THOMAS CRAVEN , ISHAQ AHTSHAM , SIMPSON MICHAEL , WILLIAMSON CRAIG , WOOD BARRY ALAN , WISCHIK CLAUDE MICHEL , HARRINGTON CHARLES ROBERT , RICKARD JANET ELIZABETH , HORSLEY DAVID , LOH YIN SZE , KHAN KARRAR AHMAD
发明人： MARSHALL COLIN , CLUNAS SCOTT , STOREY JOHN MERVYN DAVID , SINCLAIR JAMES PETER , BADDELEY THOMAS CRAVEN , ISHAQ AHTSHAM , SIMPSON MICHAEL , WILLIAMSON CRAIG , WOOD BARRY ALAN , WISCHIK CLAUDE MICHEL , HARRINGTON CHARLES ROBERT , RICKARD JANET ELIZABETH , HORSLEY DAVID , LOH YIN SZE , KHAN KARRAR AHMAD
IPC分类号： C07D279/20 , A61K31/5415 , A61P25/00
CPC分类号： A61K31/5415 , A61K9/0053 , A61K9/2095 , A61K9/2893 , A61L2/0052 , C07C303/32 , C07C309/04 , C07C309/05 , C07C309/30 , C07C309/35 , C07D279/20
摘要： The invention relates to compounds of general formula (I): wherein: each of R1 and R9 is independently selected from: -H, C1-4alkyl, C2-4alkenyl, and halogenated C1-4alkyl; each of R3NA and R3NB is independently selected from: -H, C1-4alkyl, C2-4alkenyl, and halogenated C1-4alkyl; each of R7NA and R7NB is independently selected from: -H, C1-4alkyl, C2-4alkenyl, and halogenated C1-4alkyl; and wherein: each of RA and RB is independently selected from: C1-4alkyl, halogenated C1-4alkyl, and C6-10aryl; or RA and RB are linked to form a group selected from: C1-6 alkylene and C6-10 arylene; and pharmaceutically acceptable salts thereof, which are useful in the treatment of, for example, Alzheimer's disease. In other aspects the invention also relates to novel formulations of 3,7-diamino-10H-phenothiazinium salts.
摘要翻译：本发明涉及通式（I）的化合物：其中：R 1和R 9各自独立地选自：-H，C 1-4烷基，C 2-4链烯基和卤代C 1-4烷基; R 3NA和R 3NB中的每一个独立地选自：-H，C 1-4烷基，C 2-4链烯基和卤代C 1-4烷基; R7NA和R7NB中的每一个独立地选自：-H，C 1-4烷基，C 2-4链烯基和卤代C 1-4烷基; 并且其中：RA和RB各自独立地选自：C 1-4烷基，卤代C 1-4烷基和C 6-10芳基; 或RA和RB连接形成选自以下的基团：C 1-6亚烷基和C 6-10亚芳基; 和其药学上可接受的盐，其可用于治疗例如阿尔茨海默氏病。在其它方面，本发明还涉及3,7-二氨基-10H-吩噻嗪鎓盐的新配方。

4. 发明专利

JP2013121985A 3,7-diamino-10h-phenothiazine salts and their use 有权
标题翻译： 3,7-DIAMINO-10H-PHENOTHIAZINE SALTS及其使用
公开(公告)号：JP2013121985A
公开(公告)日：2013-06-20
申请号：JP2013026635
申请日：2013-02-14
申请人： Wista Lab Ltd , ウイスタ・ラボラトリーズ・リミテッドWista Laboratories Ltd.
发明人： WISCHIK CLAUDE MICHEL , RICKARD JANET ELIZABETH , HARRINGTON CHARLES ROBERT , HORSLEY DAVID , STOREY JOHN MERVYN DAVID , MARSHALL COLIN , SINCLAIR JAMES PETER , BADDELEY THOMAS CRAVEN
IPC分类号： C07D279/20 , A61K31/5415 , A61P1/16 , A61P25/28 , A61P31/04 , A61P31/12 , A61P31/14 , A61P31/18 , A61P33/00 , A61P33/06 , A61P35/00 , A61P43/00
CPC分类号： A61K31/5415 , C07D279/20 , C07D279/22 , C09B21/00
摘要： PROBLEM TO BE SOLVED: To provide phenothiazine compounds that are useful as drugs, for example, in the treatment of tauopathies, such as Alzheimer's disease.SOLUTION: A 3,7 diamino-10H-phenothiazine compound is shown by the formula. In the formula, each of Rand Ris independently selected from -H, Calkyl, Calkenyl, and halogenated Calkyl; each of Rand Ris independently selected from -H, Calkyl, Calkenyl, and halogenated Calkyl; each of Rand Ris independently selected from -H, Calkyl, Calkenyl, and halogenated Calkyl; and each of HXand HXis independently a protic acid.
摘要翻译：待解决的问题：提供可用作药物的吩噻嗪化合物，例如用于治疗tau蛋白病如阿尔茨海默氏病。解决方案：3,7-二氨基-10H-吩噻嗪化合物由下式示出。在该公式中，R 1 和R 9 中的每一个独立地选自-H，C 3NA 和R 3NB 独立地选自-H，C 1-4 烷基，卤代C 1-4烷基，C 1-4烷基，卤代C 1-4烷基，每个R 7NA 和R 7NB 独立地选自-H，C 1-4 烷基，卤代C 1-4烷基，C 1-4烷基，卤代C 1-4烷基，并且HX 1 和HX 2 中的每一个独立地是质子酸。版权所有（C）2013，JPO＆INPIT

5. 发明专利

JP2012184244A Method of chemical synthesis and purification of diaminophenothiazinium compound including methylthioninium chloride (mtc) 审中-公开
标题翻译：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：JP2012184244A
公开(公告)日：2012-09-27
申请号：JP2012106551
申请日：2012-05-08
申请人： Wista Lab Ltd , ウィスタラボラトリーズリミテッド
发明人： STOREY JOHN MERVYN DAVID , SINCLAIR JAMES PETER , MARSHALL COLIN , TAN HAN WAN , WISCHIK CLAUDE MICHEL
IPC分类号： C07D279/18 , A61K9/20 , A61K9/48 , A61K31/5415 , A61P1/16 , A61P25/28 , A61P31/04 , A61P31/12 , A61P31/14 , A61P31/18 , A61P33/02 , A61P35/00
CPC分类号： A61K31/5415 , A61K9/0019 , A61K49/006 , C07D279/18 , C09B19/02 , G01N33/52
摘要： PROBLEM TO BE SOLVED: To provide high-purity diaminophenothiazinium compounds.SOLUTION: The high-purity diaminophenothiazinium compounds are obtained by a method of synthesis including 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) and ethylenediaminetetraacetic acid treatment (EDTAT); organic extraction (OE); and recrystallization (RX). Tablets or capsules containing the high-purity diaminophenothiazinium compounds, and pharmaceutical compositions containing the high-purity diaminophenothiazinium compounds are also provided.
摘要翻译：待解决的问题：提供高纯度的二氨基吩噻嗪鎓化合物。解决方案：通过合成方法获得高纯度二氨基吩噻嗪鎓化合物，包括以下步骤：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）; 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）和乙二胺四乙酸处理（EDTAT）之一; 有机萃取（OE）; 和重结晶（RX）。还提供了含有高纯度二氨基吩噻嗪鎓化合物的片剂或胶囊剂，以及含有高纯度二氨基吩噻嗪鎓化合物的药物组合物。版权所有（C）2012，JPO＆INPIT

6. 发明专利

JP2014055165A 3,7-diamino-10h-phenothiazine salts and their use 审中-公开
标题翻译： 3,7-DIAMINO-10H-PHENOTHIAZINE SALTS及其使用
公开(公告)号：JP2014055165A
公开(公告)日：2014-03-27
申请号：JP2013236080
申请日：2013-11-14
申请人： Wista Lab Ltd , ウイスタ・ラボラトリーズ・リミテッドWista Laboratories Ltd.
发明人： WISCHIK CLAUDE MICHEL , RICKARD JANET ELIZABETH , HARRINGTON CHARLES ROBERT , HORSLEY DAVID , STOREY JOHN MERVYN DAVID , MARSHALL COLIN , SINCLAIR JAMES PETER , BADDELEY THOMAS CRAVEN
IPC分类号： C07D279/20 , A61K31/5415 , A61P1/16 , A61P25/00 , A61P25/28 , A61P31/04 , A61P31/12 , A61P31/14 , A61P31/18 , A61P33/02 , A61P33/06 , A61P35/00
CPC分类号： A61K31/5415 , C07D279/20 , C07D279/22 , C09B21/00
摘要： PROBLEM TO BE SOLVED: To provide novel 3,7-diamino-10H-phenothiazine compounds useful in: treatment or prophylaxis of a disease caused by aggregation of proteins such as tau proteins (e.g., a neurodegenerative disease such as Alzheimer's disease), skin cancer (e.g., melanoma), a viral, bacterial or protozoal disease (e.g., Hepatitis C, HIV, West Nile Virus, or malaria), and the like; and inactivation of a pathogen in a sample (e.g., a blood or plasma sample).SOLUTION: Provided are compounds represented by the specified formula, and pharmaceutically acceptable salts, solvates and hydrates thereof. [In the formula, R, R, R, R, Rand Rare each independently selected from -H, a Calkyl, a Calkenyl, and a halogenated Calkyl; and HXand HXare each independently a protonic acid.]
摘要翻译：要解决的问题：提供新颖的3,7-二氨基-10H-吩噻嗪化合物，其用于治疗或预防由诸如tau蛋白（例如神经变性疾病如阿尔茨海默病）的蛋白质聚集引起的疾病，皮肤癌（例如黑素瘤），病毒，细菌或原生动物疾病（例如丙型肝炎，HIV，西尼罗河病毒或疟疾）等; 和样品（例如，血液或血浆样品）中病原体的失活。溶液：提供由特定式表示的化合物及其药学上可接受的盐，溶剂合物和水合物。 [式中，R，R，R，R，Rand Rare各自独立地选自-H，C烷基，Calkenyl和卤代C烷基; 和HX和HX各自独立地是质子酸。]

7. 发明专利

JP2013253095A METHODS FOR SYNTHESIS AND/OR PURIFICATION OF DIAMINOPHENOTHIAZINIUM COMPOUNDS 审中-公开
公开(公告)号：JP2013253095A
公开(公告)日：2013-12-19
申请号：JP2013171087
申请日：2013-08-21
申请人： WISTA LAB LTD
发明人： WISCHIK CLAUDE MICHEL , STOREY JOHN MERVYN DAVID , MARSHALL COLIN , SINCLAIR JAMES PETER , BADDELEY THOMAS CRAVEN
IPC分类号： C07D279/18 , A61K31/5415 , A61P25/00 , A61P25/16 , A61P25/28 , A61P31/04 , A61P31/12 , A61P31/18 , A61P33/00 , A61P35/00 , A61P43/00
摘要： PROBLEM TO BE SOLVED: To provide: methods of synthesis and/or purification of certain 3,7-diamino-phenothiazin-5-ium compounds including Methylthioninium Chloride (MTC); and further their use in methods of inactivating pathogens.SOLUTION: A method sequentially includes: producing a corresponding acylated compound; conducting deacylation, and optionally conducting purification; oxidizing the deacylated compound to obtain a diaminophenothiazinium compound; and optionally purifying diaminophenothiazinium compound.

8. 发明专利

PL3121169T3 SPOSOBY SYNTEZY I/LUB OCZYSZCZANIA ZWIĄZKÓW DIAMINOFENOTIAZYNIOWYCH 未知
公开(公告)号：PL3121169T3
公开(公告)日：2022-05-23
申请号：PL16173815
申请日：2007-07-10
申请人： WISTA LAB LTD
发明人： WISCHIK CLAUDE MICHEL , STOREY JOHN MERVYN DAVID , MARSHALL COLIN , SINCLAIR JAMES PETER , BADDELEY THOMAS CRAVEN
IPC分类号： A61K31/5415 , A61P25/28 , C07D279/18

9. 发明专利

HRP20202039T8 POSTUPCI ZA KEMIJSKU SINTEZU SUPSTITUIRANIH 10H-FENOTIAZIN-3,7-DIAMINSKIH SPOJEVA 未知
公开(公告)号：HRP20202039T8
公开(公告)日：2021-07-23
申请号：HRP20202039
申请日：2020-12-21
申请人： WISTA LAB LTD
发明人： STOREY JOHN MERVYN DAVID , LARCH CHRISTOPHER PAUL , KEMP STEPHEN JOHN , CLUNAS SCOTT , NICOLL SARAH LOUISE , GIBBARD HELEN SARAH , SIMPSON MICHAEL , SINCLAIR JAMES PETER , MARSHALL COLIN
IPC分类号： C07D279/20

10. 发明专利

ES2836492T3 Métodos de síntesis química de compuestos de 10H-fenotiazin-3,7-diamina sustituidos 未知
公开(公告)号：ES2836492T3
公开(公告)日：2021-06-25
申请号：ES16745078
申请日：2016-07-20
申请人： WISTA LAB LTD
发明人： STOREY JOHN MERVYN DAVID , LARCH CHRISTOPHER PAUL , KEMP STEVEN JOHN , CLUNAS SCOTT , NICOLL SARAH LOUISE , GIBBARD HELEN SARAH , SIMPSON MICHAEL , SINCLAIR JAMES PETER , MARSHALL COLIN
IPC分类号： C07D279/20
摘要： Un método de síntesis de un compuesto de Fórmula (1): **(Ver fórmula)** que comprende la etapa de: aminación reductora, en la que un compuesto de Fórmula (4): **(Ver fórmula)** se hace reaccionar con aldehído/cetona y un agente de aminación reductora, en condiciones de aminación reductora, para dar el compuesto correspondiente de Fórmula (1), en donde un grupo carbonilo, (O=)C

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