title: Modelling the relative metabolic occurrence of alkyl-nitrogen bond cleavage using structure-reactivity maps.
abstract: 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.
authors.affiliation: Department of Chemistry, University of Toledo, OH 43606, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Gifford
authors.forename: M A
authors.initials: MA
authors.lastname: Johnson
authors.forename: D G
authors.initials: DG
authors.lastname: Kaiser
authors.forename: C C
authors.initials: CC
authors.lastname: Tsai
mesh_terms: D001711:Biotransformation; D008744:Methylamines / Q000737:chemistry* / Q000378:metabolism*; D008956:Models, Chemical; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D008744:Methylamines