The rate of N-demethylation of N,N-dimethylanilines and N-methylanilines by rat-liver microsomes is related to their first ionization potential, their lipophilicity and to a steric bulk factor.
The N-demethylation of a series of 12 p-substituted N,N-dimethylanilines, nine m-substituted N,N-dimethylanilines, one o-substituted N,N-dimethylaniline and four p-substituted N-methylanilines by rat-liver microsomes was studied. For each compound, the apparent Vmax and Km values were determined and these parameters were correlated with their electronic, lipophilicity and steric bulk parameters reported in the literature. Multi-parameter linear regression analysis showed a good correlation between log Vmax and these parameters for the p-substituted N,N,-dimethylanilines. A lower degree of correlation was observed with the meta-substituted N,N-dimethylanilines.
D000814:Aniline Compounds / Q000378:metabolism*; D000818:Animals; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003640:Dealkylation; D066298:In Vitro Techniques; D007700:Kinetics; D008055:Lipids / Q000032:analysis; D008297:Male; D008862:Microsomes, Liver / Q000378:metabolism*; D008968:Molecular Conformation; D051381:Rats; D012995:Solubility
D000814:Aniline Compounds; D008055:Lipids; C015157:N,N-dimethylaniline; C021313:methylaniline