Single Heteroatom Substitutions in the Efavirenz Oxazinone Ring Impact Metabolism by CYP2B6.

ABSTRACT: Previously, we observed that the oxazinone ring is important for cytochrome P450 2B6 (CYP2B6) activity toward efavirenz ((4S)-6-chloro-4-(2-cyclopropylethynyl)-1,4-dihydro-4-(trifluoromethyl)-2H-3,1-benzoxazin-2-one), a CYP2B6 substrate used to treat HIV. To further understand the structural characteristics of efavirenz that render it a CYP2B6 substrate, we tested the importance of each heteroatom of the oxazinone ring. We assembled a panel of five analogues: 6-chloro-4-(2-cyclopropylethynyl)-1,4-dihydro-2-methyl-4-(trifluoromethyl)-2H-3,1-benzoxazine (1), (4S)-6-chloro-4-[(1E)-2-cyclopropylethenyl]-3,4-dihydro-4-(trifluoromethyl)-2(1H)-quinazolinone (2), (4S)-6-chloro-4-(2-cyclopropylethynyl)-3,4-dihydro-4-(trifluoromethyl)-2(1H)-quinazolinone (3), 6-chloro-4-(cyclopropylethynyl)-3,4-dihy

SUBMITTER: Cox PM 

PROVIDER: S-EPMC5155582 | biostudies-literature | 2016 Dec

REPOSITORIES: biostudies-literature