Optimization of benzyloxazoles as non-nucleoside inhibitors of HIV-1 reverse transcriptase to enhance Y181C potency

Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved activity towards Tyr181Cys containing variants was pursued with the assistance of free energy perturbation (FEP) calculations. Optimization of the 4-R substituent in 1 led to ethyl and isopropyl analogs 1e and 1f with 1...

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Detalles Bibliográficos
Autores: Bollini, Mariela, Gallardo Macias, Ricardo, Spasov, Krasimir A., Tirado Rives, Julian, Anderson, Karen S., Jorgensen, William L.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2012
País:Argentina
Institución:Consejo Nacional de Investigaciones Científicas y Técnicas
Repositorio:CONICET Digital (CONICET)
Idioma:inglés
OAI Identifier:oai:ri.conicet.gov.ar:11336/22884
Acceso en línea:http://hdl.handle.net/11336/22884
Access Level:acceso abierto
Palabra clave:Anti-Hiv Agents
Computer-Aided Drug Design
Free-Energy Calculations
Nnrtis
https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
Descripción
Sumario:Design of non-nucleoside inhibitors of HIV-1 reverse transcriptase with improved activity towards Tyr181Cys containing variants was pursued with the assistance of free energy perturbation (FEP) calculations. Optimization of the 4-R substituent in 1 led to ethyl and isopropyl analogs 1e and 1f with 1–7 nM potency towards both the wild-type virus and a Tyr181C variant.

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