7-Step Flow Synthesis of the HIV Integrase Inhibitor Dolutegravir
نویسندگان
چکیده
منابع مشابه
The activity of the integrase inhibitor dolutegravir against HIV-1 variants isolated from raltegravir-treated adults.
BACKGROUND Dolutegravir (DTG, S/GSK1349572) is an integrase inhibitor with low nanomolar potency. Susceptibility to dolutegravir and raltegravir was determined for raltegravir-resistant clinical isolates. METHODS Genotypic and phenotypic susceptibility to integrase inhibitors was examined using 39 clinical isolate samples obtained from 18 adults who had exhibited incomplete viral suppression ...
متن کاملMetabolism, excretion, and mass balance of the HIV-1 integrase inhibitor dolutegravir in humans.
The pharmacokinetics, metabolism, and excretion of dolutegravir, an unboosted, once-daily human immunodeficiency virus type 1 integrase inhibitor, were studied in healthy male subjects following single oral administration of [(14)C]dolutegravir at a dose of 20 mg (80 μCi). Dolutegravir was well tolerated, and absorption of dolutegravir from the suspension formulation was rapid (median time to p...
متن کاملDolutegravir: a next-generation integrase inhibitor for treatment of HIV infection.
Dolutegravir (DTG), a next-generation integrase strand transfer inhibitor (INSTI), was recently approved for use in the treatment of human immunodeficiency virus infection. In treatment-naive trial participants, DTG given at 50 mg once daily without pharmacologic boosting combined with a standard nucleoside backbone was shown to be noninferior or superior to first-line regimens containing efavi...
متن کاملRelative bioavailability of a paediatric granule formulation of the HIV integrase inhibitor dolutegravir in healthy adult subjects.
BACKGROUND This study evaluated the pharmacokinetics of a granule formulation of dolutegravir developed as an alternative to tablets for use in paediatric populations. METHODS A randomized, open-label study in healthy adults was carried out. Subjects received five treatments in a crossover design: a single dose of dolutegravir 50 mg as a tablet and dolutegravir 50 mg in 10 g of granule admini...
متن کاملStructural and functional analyses of the second-generation integrase strand transfer inhibitor dolutegravir (S/GSK1349572).
Raltegravir (RAL) and related HIV-1 integrase (IN) strand transfer inhibitors (INSTIs) efficiently block viral replication in vitro and suppress viremia in patients. These small molecules bind to the IN active site, causing it to disengage from the deoxyadenosine at the 3' end of viral DNA. The emergence of viral strains that are highly resistant to RAL underscores the pressing need to develop ...
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ژورنال
عنوان ژورنال: Angewandte Chemie International Edition
سال: 2018
ISSN: 1433-7851
DOI: 10.1002/anie.201802256