RESUMEN
Analogs of (E)-5-(2-bromovinyl)-2'-deoxycytidine (BrVdCyd) (1) by substitution at N(4) were synthesized to impart resistance against deamination. The anti-HSV-1 activity and solution conformation of these analogs were determined. N(4)-Acetyl-BrVdCyd (2) was a potent inhibitor of HSV-1 replication whereas N(4)-propanoyl-BrVdCyd (3) had good activity and N(4)-Butanoyl-BrVdCyd (4) had only low activity against HSV-1 replication. N(4)-Methyl-BrVdCyd (5) was devoid of activity against HSV-1.
Asunto(s)
Antivirales/química , Antivirales/farmacología , Bromodesoxicitidina/análogos & derivados , Simplexvirus/efectos de los fármacos , Antivirales/síntesis química , Bromodesoxicitidina/química , Bromodesoxicitidina/farmacología , Conformación de Carbohidratos , Línea Celular , Estabilidad de Medicamentos , Humanos , Pruebas de Sensibilidad Microbiana , Replicación Viral/efectos de los fármacosRESUMEN
Analogs of 5-methoxymethyl-2'-deoxycytidine, MMdCyd (1) by substitution at N4 were synthesized to impart resistance against deamination. The anti HSV-1 activity and solution conformation of analogs were determined. N4-Butanoyl-MMdCyd (10) was a potent inhibitor of HSV-1 replication while N4-hexanoyl-MMdCyd (11), N4-propanoyl-MMdCyd (9) and N4-acetyl-MMdCyd (8) had good activity against HSV-1 replication. All other analogs were devoid of activity against HSV-1.