Modelling the relative metabolic occurrence of alkyl-nitrogen bond cleavage using structure-reactivity maps.
Over a broad range of tertiary N-methyl amines, whenever alkyl-nitrogen bond cleavage was observed, N-demethylation was also observed. Alkyl-nitrogen bond cleavage in rings, alkyl-nitrogen bond cleavage if the carbon of the N-dealkylation reaction-site is in a ring and the nitrogen atom of the reaction-site is not in a ring, and dedimethylamination are not likely to occur relative to N-demethylation. Structure-reactivity relationships for other N-dealkylations, such as N-debenzylation, N-dethiophenation, and N-dedimethylaminoethylation of tertiary amines were evident from a visual inspection of the structure-reactivity map. Structure-reactivity maps proved to be a useful tool for ascertaining structural environments influencing the relative occurrence of alkyl-nitrogen bond cleavage in tertiary N-methyl amines.
Gifford
E M
EM
Department of Chemistry, University of Toledo, OH 43606, USA.
Johnson
M A
MA
Kaiser
D G
DG
Tsai
C C
CC
D001711:Biotransformation; D008744:Methylamines / Q000737:chemistry* / Q000378:metabolism*; D008956:Models, Chemical; D015394:Molecular Structure; D013329:Structure-Activity Relationship
D008744:Methylamines