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Synthesis and preliminary in vitro metabolic studies on N,N ‐dimethyl‐ N′ ‐2‐imidazolyl‐ N ′‐benzyl‐1,2‐ethanediamine, an analog of the carcinogenic antihistamine methapyrilene
Author(s) -
Compernolle F.,
Castagnoli N.
Publication year - 1982
Publication title -
journal of heterocyclic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.321
H-Index - 59
eISSN - 1943-5193
pISSN - 0022-152X
DOI - 10.1002/jhet.5570190630
Subject(s) - chemistry , iminium , imidazole , amide , ring (chemistry) , metabolite , methylene , stereochemistry , acylation , medicinal chemistry , alkylation , carcinogen , organic chemistry , ion , biochemistry , catalysis
This paper describes the synthesis and preliminary metabolic studies on N,N ‐dimethyl‐ N ′‐2‐imidazolyl‐ N ′‐benzyl‐1,2‐ethanediamine (compound 12 ), an imidazole analog of the carcinogenic antihistamine methapyrilene. The 2‐aminoimidazole starting material is carried through a five‐step reaction sequence which involves introduction of the benzyl and dimethylaminoethyl side chains via sequential acylation of the 2‐amino group and reduction of each intermediate amide. Metabolic studies on compound 12 and a d 2 ‐analog were performed with rabbit liver microsomes. Chemical ionization mass spectral analysis indicates the presence of metabolites formed by N ‐demethylation and imidazole C‐oxidation. In addition, a seven membered ring metabolite has been identified which apparently is formed by intramolecular cyclization of an intermediate methylene iminium ion.