RESUMEN
A series of 5,6,7,8-tetrahydro-1,6-naphthyridine derivatives targeting the allosteric lens-epithelium-derived-growth-factor-p75 (LEDGF/p75)-binding site on HIV-1 integrase, an attractive target for antiviral chemotherapy, was prepared and screened for activity against HIV-1 infection in cell culture. Small molecules that bind within the LEDGF/p75-binding site promote aberrant multimerization of the integrase enzyme and are of significant interest as HIV-1-replication inhibitors. Structure-activity-relationship studies and rat pharmacokinetic studies of lead compounds are presented.
Asunto(s)
Inhibidores de Integrasa VIH/farmacología , VIH-1/efectos de los fármacos , Naftiridinas/farmacología , Sitio Alostérico , Cristalografía por Rayos X , Infecciones por VIH/tratamiento farmacológico , Inhibidores de Integrasa VIH/química , Inhibidores de Integrasa VIH/uso terapéutico , VIH-1/enzimología , VIH-1/fisiología , Humanos , Naftiridinas/química , Naftiridinas/uso terapéutico , Replicación Viral/efectos de los fármacosRESUMEN
Concerns about uncontrolled hazardous waste sites and other sources of unplanned releases of hazardous substances into the environment are wide ranging. Specific concerns regarding hazardous waste sites include harm to human health, expensive clean-up costs, depreciated property values, and ecological damage. This paper focuses on the level of hazard and toxicologic import of those Superfund sites with completed exposure pathways.Published in Reviews on Environmental Health, Vol. 12, No. 4, pp. 235-251, 1997.
