Synthesis of certain hydroxy analogues of the antimalarial drug primaquine and their in vitro methemoglobin-producing and glutathione-depleting activity in human erythrocytes.

A number of hydroxy analogues of the antimalarial drug primaquine [8-[(4-amino-1-methylbutyl)amino]-6-methoxyquinoline] were synthesized and characterized by 1H NMR and mass spectra. Several of the compounds were found to be active in forming methemoglobin in human erythrocytes, particularly in those from glucose-6-phosphate dehydrogenase (G6PD) deficient subjects. Decreased levels of glutathione (GSH) in G6PD-deficient erythrocytes were also found with compounds that were active methemoglobin formers.