Pyrimethamine salts

Table 2 Repository antimalarial activity of pyrimethamine salts against P. berghei in mice 36, 74,...

Repository action of miscellaneous pyrimethamine salts 136,103-105,107 against P. berghei in... 

The universal use of common salt has allowed it to be used as a vehicle for combating widespread iodine deficiency by fortifying the salt with iodine, and fluoride has also been added as a preventive measure against dental caries. Chloroquine or pyrimethamine salt mixtures have been used to suppress the sporozoites responsible for vivax malaria. 

With regard to the possible use of ivermectin for tsetse and tick control in Africa, a light-stable formulation of MK933, or MK936, the less expensive precursor, might find application for the treatment of domestic and even wild animals if the drug were to be offered in combination with a coccidiostat like Pancoxin (sulphaquinoxaline and pyrimethamine) in a salt lick block (7 ). 

The synthesis of MZP is shown in Scheme 3.1. Nitration of the readily available antimalarial diaminopyrimidine pyrimethamine (PYM) (113) yielded w-nitropyrimethamine (MNP) (114) exclusively, and reduction to the corresponding amine w-aminopyrimethamine (MAP) (115), followed by diazotisation and azidation afforded the azide (111) in excellent overall yield [135, 136]. The extremely poor aqueous solubility of MZP (22 4/water-soluble salt for biological evaluation, and m-azidopyrimethamine ethanesulphonate MZPES (112), with an aqueous solubility of 17.60 0.45 mg/ml at 20°C, was the most appropriate for this purpose. A series of derivatives (116)-(123), differing... 

Besides synthesis of pharmaceutical co-crystals, mechanosynthesis has been successfully applied to the synthesis of pharmaceutical salts. Trask et al. have demonstrated mechanochemical screening for pharmaceutical salts by grinding the model API molecules trimethoprim and pyrimethamine with seven pharmaceutically acceptable carboxylic acids formic, acetic, maleic, fumaric, succinic, glutaric and salicylic. The results of screening experiments (Table 8.2) demonstrate that LAG is more versatile than neat grinding in screening for pharmaceutical salts. More importantly, the application of mechanochemical techniques not only led to the formation of already reported salt forms but also enabled the discovery of 14 new salt forms. 

Table 8.2 Results of mechanochemical salt screening for pyrimethamine. ...

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