公开(公告)号：US20210322435A1

公开(公告)日：2021-10-21

申请号：US17355336

申请日：2021-06-23

申请人： Wis Ta Laboratories Ltd.

发明人： Claude Michel Wischik ,  John Mervy David Storey ,  Colin Marshall ,  James Peter Sinclair ,  Thomas Craven Baddeley

IPC分类号： A61K31/5415 ,  C07D279/18 ,  C07D279/20

摘要： 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.

公开(公告)号：US20140221359A1

公开(公告)日：2014-08-07

申请号：US14248730

申请日：2014-04-09

申请人： Wis Ta Laboratories Ltd.

发明人： Claude Michel WISCHIK ,  Janet Elizabeth Rickard ,  Charles Robert Harrington ,  David Horsley ,  John Mervyn David Storey ,  Colin Marshall ,  James Peter Sinclair ,  Thomas Craven Baddeley

IPC分类号： C07D279/20

CPC分类号： C07D279/20 ,  A61K31/5415 ,  A61K49/0002 ,  A61K49/003 ,  A61K51/0465 ,  G01N33/6896 ,  G01N2800/2835 ,  Y02A50/393 ,  Y02A50/411

摘要： Described are methods of prepraing reduced 3,7-diamino-10H-phenothiazine (DAPTZ) compounds of formula: wherein: R1 and R9 are 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; each of HX1 and HX2 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.

摘要翻译： 描述了制备下式的还原的3,7-二氨基-10H-吩噻嗪（DAPTZ）化合物的方法：其中：R 1和R 9独立地选自：-H; C 1-4烷基; C2-4烯基; 和卤代C 1-4烷基; R3NA和R3NB中的每一个独立地选自：-H; C 1-4烷基; C2-4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; C2-4烯基; 和卤代C 1-4烷基; HX1和HX2各自独立地是质子酸; 及其药学上可接受的盐，溶剂化物和水合物。 这些方法对于生产稳定的还原形式和高纯度特别有用。 稳定性和纯度与治疗疾病的药物组合物特别相关。 该化合物可用于治疗例如 tau病，如阿尔茨海默病，以及相应的氧化型硫堇药物的前药。