1. 4,1-Benzoxazepinone analogues of efavirenz (Sustiva) as HIV-1 reverse transcriptase inhibitors.
- Author
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Cocuzza AJ, Chidester DR, Cordova BC, Klabe RM, Jeffrey S, Diamond S, Weigelt CA, Ko SS, Bacheler LT, Erickson-Viitanen SK, and Rodgers JD
- Subjects
- Alkynes, Animals, Benzoxazines, Cyclopropanes, HIV Reverse Transcriptase genetics, Humans, Macaca mulatta, Oxazines chemistry, Oxazines pharmacokinetics, Protein Binding, Quinazolines chemistry, Quinazolines pharmacokinetics, Quinazolines pharmacology, Quinazolinones, Reverse Transcriptase Inhibitors chemistry, Reverse Transcriptase Inhibitors pharmacokinetics, Structure-Activity Relationship, HIV Reverse Transcriptase antagonists & inhibitors, Oxazines pharmacology, Reverse Transcriptase Inhibitors pharmacology
- 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.
- Published
- 2001
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