RESUMO
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.
Assuntos
Inibidores de Integrase de HIV/farmacologia , HIV-1/efeitos dos fármacos , Naftiridinas/farmacologia , Sítio Alostérico , Cristalografia por Raios X , Infecções por HIV/tratamento farmacológico , Inibidores de Integrase de HIV/química , Inibidores de Integrase de HIV/uso terapêutico , HIV-1/enzimologia , HIV-1/fisiologia , Humanos , Naftiridinas/química , Naftiridinas/uso terapêutico , Replicação Viral/efeitos dos fármacosRESUMO
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.
