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 C1-4
alkyl; 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.