Synthesis and in vitro activity of heterocyclic inhibitors of CYP2A6 and CYP2A13, two cytochrome P450 enzymes present in the respiratory tract.
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.
Department of Chemistry, University of Basel, St.-Johanns-Ring 19, 4052 Basel, Switzerland.
Antoinette
A
Chougnet
Wolf-D
WD
Woggon
Esther
E
Locher
Boris
B
Schilling
D001189:Aryl Hydrocarbon Hydroxylases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D065637:Cytochrome P-450 CYP2A6; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012137:Respiratory System / Q000201:enzymology* / Q000378:metabolism
D004791:Enzyme Inhibitors; D006571:Heterocyclic Compounds; D007093:Imidazoles; D001189:Aryl Hydrocarbon Hydroxylases; C585710:CYP2A6 protein, human; D065637:Cytochrome P-450 CYP2A6