P450 interaction with HIV protease inhibitors: relationship between metabolic stability, inhibitory potency, and P450 binding spectra.
作者： James R. Tata , Kevin Chapman , Jiunn H. Lin , Lixia Jin , Masato Chiba
DOI:
关键词: Protease inhibitor (pharmacology) 、 In vitro 、 Stereochemistry 、 HIV Protease Inhibitor 、 Enzyme inhibitor 、 Biology 、 Microsome 、 Biochemistry 、 CYP3A4 、 Metabolism 、 Cytochrome P450
摘要: More than 60 human immunodeficiency virus protease inhibitors were examined for the structure-activity relationship between metabolic stability, CYP3A4 inhibitory potency, and substrate-induced binding spectra with a ferric form of P450 in liver microsomes. A positive was found potency stability; namely, compounds that more potent inhibition generally metabolically stable. In addition, formed two clusters defined by distinct type spectra: II stable those I spectra. The suggested presence position heterocyclic nitrogen on pyridine moiety play an important role determining manner interaction magnitude inhibition/metabolic stability series structurally related under development.
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