An analysis of the relative occurrence of N-demethylation and N-oxidation in xenobiotic metabolism using structure-reactivity maps.
The relative occurrence of N-demethylation and N-oxidation in a structurally diverse set of N-methyl tertiary amines was examined using structure-reactivity maps. A structure-reactivity map of the data indicated important structural features useful for predicting the relative occurrence of these reactions. A steric index which describes the degree of steric hinderance at the N-methyl reaction site is defined. A QSAR between the relative occurrence of N-demethylation and N-oxidation of N-methyl tertiary amines and the steric index was developed.
Gifford
E M
EM
Department of Chemistry, Kent State University, OH 44242, USA
Johnson
M A
MA
Kaiser
D G
DG
Tsai
C C
CC
D000818:Animals; D001711:Biotransformation; D006801:Humans; D016014:Linear Models; D008745:Methylation; D008861:Microsomes / Q000378:metabolism; D008956:Models, Chemical; D008958:Models, Molecular; D010084:Oxidation-Reduction; D051381:Rats; D013329:Structure-Activity Relationship; D015262:Xenobiotics / Q000737:chemistry / Q000378:metabolism*
D015262:Xenobiotics