title: Benzothiadiazine dioxide human cytomegalovirus inhibitors: synthesis and antiviral evaluation of main heterocycle modified derivatives.
abstract: The benzothiadiazine dioxide derivatives are potent non-nucleoside human cytomegalovirus (HCMV) inhibitors. As part of our comprehensive structure-activity relationship (SAR) study of these compounds, we have now proposed structural modifications on the heterocyclic moiety both on the number and the nature of the fused heterocycle and on the kind of heteroatoms present on it. Synthesis of these new compounds (benzyl derivatives of thiadiazines, thienothiadiazines, benzothienothiadiazines and quinazolines) and the antiviral evaluation against HCMV has been performed. SAR investigation on this class of compounds has defined the structural requirements for potency and toxicity. They have revealed two important clues: i) a fused ring to the thiadiazine framework is necessary to maintain the anti-HCMV action, and ii) the sulfamido moiety in the main heterocycle is crucial to avoid cytotoxicity.
authors.affiliation: Instituto de Química Médica (CSIC), Madrid, Spain. amartinez@neuropharma.es
authors.forename: Ana
authors.initials: A
authors.lastname: Martinez
authors.forename: Carmen
authors.initials: C
authors.lastname: Gil
authors.forename: Ana
authors.initials: A
authors.lastname: Castro
authors.forename: Ana M
authors.initials: AM
authors.lastname: Bruno
authors.forename: Concepción
authors.initials: C
authors.lastname: Pérez
authors.forename: Columbiana
authors.initials: C
authors.lastname: Prieto
authors.forename: Joaquin
authors.initials: J
authors.lastname: Otero
mesh_terms: D000998:Antiviral Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001581:Benzothiadiazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D003587:Cytomegalovirus / Q000187:drug effects* / Q000378:metabolism; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000821:virology; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015394:Molecular Structure; D011799:Quinazolines / Q000138:chemical synthesis / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000998:Antiviral Agents; D001581:Benzothiadiazines; D011799:Quinazolines