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Synthesis and in vitro Activity of Heterocyclic Inhibitors of CYP2A6 and CYP2A13, Two Cytochrome P450 Enzymes Present in the Respiratory Tract
Author(s) -
Chougnet Antoinette,
Woggon WolfD.,
Locher Esther,
Schilling Boris
Publication year - 2009
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.200800712
Subject(s) - cyp2a6 , enzyme , chemistry , cytochrome p450 , stereochemistry , in vitro , respiratory tract , biochemistry , cyp3a4 , respiratory system , biology , anatomy
To be sniffed at : Several 1‐ and 2‐substituted 1 H ‐imidazoles and 2‐substituted oxazoles, oxazolines and pyrazines have been synthesized and tested as inhibitors of the cytochrome P450 enzymes CYP2A6 and CYP2A13. 1‐Substituted 1 H ‐imidazoles bearing short chains (pentyl, hexyl or hexenyl) were found to be potent inhibitors of both enzymes, and showed IC 50 values of about 2 μ M .The synthesis of several heterocyclic compounds (1‐ or 2‐substituted 1H ‐imidazoles and 2‐substituted oxazoles, oxazolines and pyrazines) has been achieved. These compounds were tested as inhibitors of CYP2A6 and CYP2A13—two cytochrome P450 enzymes present in the respiratory tract—with a view to preventing the formation of carcinogenic metabolites of nicotine and inhibiting the metabolism of fragrances. 1‐Substituted imidazoles bearing short alkyl chains displayed IC 50 values of around 2 μ M for both enzymes, together with high vapour pressures.