Benzothiadiazine dioxides (BTD) derivatives as non-nucleoside human cytomegalovirus (HCMV) inhibitors. study of structural requirements for biological activity.
Two new series of BTD derivatives have been synthesised allowing to explore the steric requirements for their biological activity. The N3-alkylBTD compounds have shown antiviral activity in the same order or lower than previously prepared compounds. However, the cytotoxicity values observed prevent this new series of BTD derivatives from its potential therapeutic application. Concerning BTD derivatives with the modified linker attached to N1 position, we have obtained new non-nucleoside anti-HCMV derivatives. The activity against HCMV is shown at concentrations that were 10-fold lower than the concentration that was toxic for the host cells, which confirm that these derivatives show a specific antiviral effect against HCMV. SAR conclusions derived from these last compounds have provided new knowledge about the structural requirements of BTD showing certain positions that could be modified for enhancing the anti-HCMV action.
Instituto de Qui;mica Médica (CSIC), Juan de la Cierva 3, 28006, Madrid, Spain. amartinez@neuropharma.es
Ana
A
Martinez
Carmen
C
Gil
Ana
A
Castro
Concepción
C
Pérez
Columbiana
C
Prieto
Joaquin
J
Otero
D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001581:Benzothiadiazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003587:Cytomegalovirus / Q000187:drug effects*; D003588:Cytopathogenic Effect, Viral; D006577:Heterocyclic Oxides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D013329:Structure-Activity Relationship; D010948:Viral Plaque Assay
D000998:Antiviral Agents; D001581:Benzothiadiazines; D006577:Heterocyclic Oxides