Synthesis and pharmacokinetic profile of highly deuterated brecanavir analogs
| Autor: | Emile J. Velthuisen, Todd M. Baughman, Brian A. Johns, David P. Temelkoff, Jason G. Weatherhead |
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| Rok vydání: | 2013 |
| Předmět: |
Metabolic Clearance Rate
Stereochemistry Bond breaking chemistry.chemical_compound Pharmacokinetics Drug Discovery Kinetic isotope effect medicine Animals Humans Benzodioxoles Pharmacology Molecular Structure Organic Chemistry HIV Protease Inhibitors General Medicine Metabolic stability Deuterium Rate-determining step Combinatorial chemistry Protease inhibitor (biology) Rats Models Chemical chemistry Area Under Curve Hepatocytes Brecanavir Administration Intravenous Carbamates medicine.drug |
| Zdroj: | European Journal of Medicinal Chemistry. 63:202-212 |
| ISSN: | 0223-5234 |
| DOI: | 10.1016/j.ejmech.2013.02.001 |
| Popis: | Several highly deuterated analogs of the HIV-1 protease inhibitor brecanavir have been prepared to study the effect of deuterium upon metabolic stability. The sites for deuterium incorporation were initially chosen to maximize the potential for a kinetic isotope effect; locations where C–H bond breaking is the rate limiting step. The analogs have been profiled in both in vitro and in vivo pharmacokinetic studies and the result will be described herein. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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