Methods of chemical synthesis and purification of diaminophenothiazinium compounds including methylthioninium chloride (MTC)

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EP 2 322 517 A8

(12)	CORRECTED EUROPEAN PATENT APPLICATION
	Note: Bibliography reflects the latest situation

(15)	Correction information:
	Corrected version no 1 (W1 A1)

(48)	Corrigendum issued on:
	13.07.2011 Bulletin 2011/28

(43)	Date of publication:
	18.05.2011 Bulletin 2011/20

(21)	Application number: 10010049.4

(22)	Date of filing: 21.09.2005

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International Patent Classification (IPC):

C07D 279/18^(2006.01)
A61P 35/00^(2006.01)

A61K 31/54^(2006.01)
A61P 25/28^(2006.01)

(84)	Designated Contracting States:
	AT BE BG CH CY CZ DE DK EE ES FI FR GB GR HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI SK TR
	Designated Extension States:
	AL BA HR MK YU

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Priority:

23.09.2004 GB 0421234
17.02.2005 GB 0503343
07.09.2005 WO PCT/GB2005/003441

(62)	Application number of the earlier application in accordance with Art. 76 EPC:
	05783989.6 / 1799662

(71)	Applicant: Wista Laboratories Ltd.
	Singapore 139948 (SG)

(72)	Inventors:
	Storey, John Mervyn David Strathcarron Ross-shire IV54 8YL (GB) Sinclair, James Peter Old Aberdeen AB24 3UE (GB) Marshall, Colin Old Aberdeen AB24 3UE (GB) Tan, Han Wan Singapore 160073 Singapore (SG) Wischik, Claude Michel Old Aberdeen Aberdeenshire AB24 1RQ (GB)

(74)	Representative: Wytenburg, Wilhelmus Johannes et al
	Mewburn Ellis LLP 33 Gutter Lane London EC2V 8AS London EC2V 8AS (GB)


	Remarks:
	This application was filed on 21-09-2010 as a divisional application to the application mentioned under INID code 62.

(54)	Methods of chemical synthesis and purification of diaminophenothiazinium compounds including methylthioninium chloride (MTC)

(57) 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 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.