Structure-activity relationships in the formation of amides from substituted N-benzylanilines. 1994

M Ulgen, and J W Gorrod, and D Barlow
Chelsea Department of Pharmacy, King's College London, University of London, UK.

1. The in vitro hepatic microsomal metabolism of certain substituted N-benzylanilines was studied in the male hamster to establish the mechanism(s) and process(es) involved in the formation of the corresponding amides. 2. N-Benzyl-2,4,6-trihalogeno, N-benzyl-4-cyano- and N-benzyl-4-nitroanilines were only metabolized by N-debenzylation. However, N-benzyl-4-methyl- and N-benzyl-2,4,6-trimethylanilines gave rise to both the corresponding amide and nitrone metabolites together with dealkylation products. These latter two substrates also produced hydroxymethyl metabolites as major products. Metabolism of N-(2,4,6,-trimethylbenzyl)aniline also led to the formation of an amide metabolite. The dealkylation products, the corresponding imine and an unknown metabolite, probably an hydroxylated product were also detected with this substrate. 3. N-(2,4-Dichlorobenzyl) and N-(2,6-dichlorobenzyl) anilines yielded the corresponding nitrone metabolites; but no amide metabolite was detected. Oxidative dealkylation leading to the formation of the corresponding primary anilines and aldehydes, together with para hydroxylation of aniline rings, were established as major routes of metabolism for both compounds. Similarly, neither N-(2,4,6-trifluorobenzyl) nor N-(4-nitrobenzyl) anilines produced any amide metabolite although dealkylation products were detected. 4. The pattern of amide formation observed for these N-benzylsubstituted anilines is discussed in terms of the steric and electronic effects of their aromatic substituents.

UI MeSH Term Description Entries
D008297 Male Males
D008647 Mesocricetus A genus in the order Rodentia and family Cricetidae. One species, Mesocricetus auratus or golden hamster is widely used in biomedical research. Hamsters, Golden,Hamsters, Golden Syrian,Hamsters, Syrian,Mesocricetus auratus,Syrian Golden Hamster,Syrian Hamster,Golden Hamster,Golden Hamster, Syrian,Golden Hamsters,Golden Syrian Hamsters,Hamster, Golden,Hamster, Syrian,Hamster, Syrian Golden,Syrian Hamsters
D008862 Microsomes, Liver Closed vesicles of fragmented endoplasmic reticulum created when liver cells or tissue are disrupted by homogenization. They may be smooth or rough. Liver Microsomes,Liver Microsome,Microsome, Liver
D008958 Models, Molecular Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures. Molecular Models,Model, Molecular,Molecular Model
D002851 Chromatography, High Pressure Liquid Liquid chromatographic techniques which feature high inlet pressures, high sensitivity, and high speed. Chromatography, High Performance Liquid,Chromatography, High Speed Liquid,Chromatography, Liquid, High Pressure,HPLC,High Performance Liquid Chromatography,High-Performance Liquid Chromatography,UPLC,Ultra Performance Liquid Chromatography,Chromatography, High-Performance Liquid,High-Performance Liquid Chromatographies,Liquid Chromatography, High-Performance
D002855 Chromatography, Thin Layer Chromatography on thin layers of adsorbents rather than in columns. The adsorbent can be alumina, silica gel, silicates, charcoals, or cellulose. (McGraw-Hill Dictionary of Scientific and Technical Terms, 4th ed) Chromatography, Thin-Layer,Thin Layer Chromatography,Chromatographies, Thin Layer,Chromatographies, Thin-Layer,Thin Layer Chromatographies,Thin-Layer Chromatographies,Thin-Layer Chromatography
D006224 Cricetinae A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS. Cricetus,Hamsters,Hamster
D000577 Amides Organic compounds containing the -CO-NH2 radical. Amides are derived from acids by replacement of -OH by -NH2 or from ammonia by the replacement of H by an acyl group. (From Grant & Hackh's Chemical Dictionary, 5th ed) Amide
D000814 Aniline Compounds Compounds that include the aminobenzene structure. Phenylamine,Phenylamines,Anilines,Compounds, Aniline
D000818 Animals Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA. Animal,Metazoa,Animalia

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