Invention Grant
US07790881B2 Methods of chemical synthesis and purification of diaminophenothiazinium compounds including methylthioninium chloride (MTC)
有权
二氨基吩噻嗪鎓化合物的化学合成和纯化方法,包括甲基硫堇(MTC)
- Patent Title: Methods of chemical synthesis and purification of diaminophenothiazinium compounds including methylthioninium chloride (MTC)
- Patent Title (中): 二氨基吩噻嗪鎓化合物的化学合成和纯化方法,包括甲基硫堇(MTC)
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Application No.: US11575845Application Date: 2005-09-21
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Publication No.: US07790881B2Publication Date: 2010-09-07
- Inventor: John Mervyn David Storey , James Peter Sinclair , Colin Marshall , Han Wan Tan
- Applicant: John Mervyn David Storey , James Peter Sinclair , Colin Marshall , Han Wan Tan
- Applicant Address: SG Singapore
- Assignee: Wista Laboratories Ltd.
- Current Assignee: Wista Laboratories Ltd.
- Current Assignee Address: SG Singapore
- Agency: Foley & Lardner LLP
- Priority: GB0421234.6 20040923; GB0503343.6 20050217; WOPCT/GB2005/003441 20050907
- International Application: PCT/GB2005/003634 WO 20050921
- International Announcement: WO2006/032879 WO 20060330
- Main IPC: C07D279/20
- IPC: C07D279/20 ; A61K31/5415

Abstract:
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 R1 and R9 is independently selected from: —H; C1-4 alkenyl; and halogenated C1-4alkyl; each of R3NA and R3NB is independently selected from: C1-4 alkyl; C2-4alkenyl; and halogenated C4-1 alkyl; each of R7NA and R7NB is independently selected from: C1-4 alkyl; C2-4alkenyl; and halogenated C1-4 alkyl; and X is one or more anionic counter ions to achieve electrical neutrality.
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