Abstract
A series of 4,1-benzoxazepinone analogues of efavirenz (Sustiva) as potent NNRTIs has been discovered. The cis-3-alkylbenzoxazepinones are more potent then the trans isomers and can be synthesized preferentially by a novel stereoselective cyclization. The best compounds are potent orally bioavailable inhibitors of both wild-type HIV-1 and its clinically relevant K103N mutant virus, but are highly protein-bound in human plasma.
MeSH terms
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Alkynes
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Animals
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Benzoxazines
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Cyclopropanes
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HIV Reverse Transcriptase / antagonists & inhibitors*
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HIV Reverse Transcriptase / genetics
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Humans
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Macaca mulatta
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Oxazines / chemistry
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Oxazines / pharmacokinetics
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Oxazines / pharmacology*
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Protein Binding
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Quinazolines / chemistry
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Quinazolines / pharmacokinetics
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Quinazolines / pharmacology
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Quinazolinones
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Reverse Transcriptase Inhibitors / chemistry
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Reverse Transcriptase Inhibitors / pharmacokinetics
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Reverse Transcriptase Inhibitors / pharmacology*
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Structure-Activity Relationship
Substances
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Alkynes
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Benzoxazines
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Cyclopropanes
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DPC 961
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Oxazines
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Quinazolines
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Quinazolinones
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Reverse Transcriptase Inhibitors
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HIV Reverse Transcriptase
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efavirenz