Methaemoglobin formation by aromatic amines

Abstract Methaemoglobin formation induced in cats by many substituted anilines has been investigated in an attempt to correlate chemical structure with activity. Although no precise relation emerged, some generalizations could be made. 4-Substituents (except methyl and methoxy) increased the activity of aniline. The activity of aniline was either unaltered or reduced by 2- and 3-substituents. Polyhalo-, polymethyl-, methoxy-, ethoxy- and carboxyester substituents reduced activity, and carboxy groups abolished it. Steric effects around the amino-group were not important. The activities of the compounds are discussed in relation to their absorption, distribution, metabolic transformation and the activities of their metabolites.