Synthesis and in vitro activity of heterocyclic inhibitors of CYP2A6 and CYP2A13, two cytochrome P450 enzymes present in the respiratory tract

Antoinette Chougnet; Wolf-D Woggon; Esther Locher; Boris Schilling

doi:10.1002/cbic.200800712

Synthesis and in vitro activity of heterocyclic inhibitors of CYP2A6 and CYP2A13, two cytochrome P450 enzymes present in the respiratory tract

Chembiochem. 2009 Jun 15;10(9):1562-7. doi: 10.1002/cbic.200800712.

Authors

Antoinette Chougnet¹, Wolf-D Woggon, Esther Locher, Boris Schilling

Affiliation

¹ Department of Chemistry, University of Basel, St.-Johanns-Ring 19, 4052 Basel, Switzerland.

PMID: 19434638
DOI: 10.1002/cbic.200800712

Abstract

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 microM for both enzymes, together with high vapour pressures.

MeSH terms

Aryl Hydrocarbon Hydroxylases / antagonists & inhibitors*
Aryl Hydrocarbon Hydroxylases / metabolism
Cytochrome P-450 CYP2A6
Enzyme Inhibitors / chemical synthesis*
Enzyme Inhibitors / chemistry
Enzyme Inhibitors / pharmacology
Heterocyclic Compounds / chemical synthesis*
Heterocyclic Compounds / chemistry
Heterocyclic Compounds / pharmacology
Humans
Imidazoles / chemical synthesis
Imidazoles / chemistry
Imidazoles / pharmacology
Respiratory System / enzymology*
Respiratory System / metabolism

Substances

Enzyme Inhibitors
Heterocyclic Compounds
Imidazoles
Aryl Hydrocarbon Hydroxylases
CYP2A6 protein, human
Cytochrome P-450 CYP2A6