Synthesis, antimalarial activity, structure–activity relationship analysis of thieno-[3,2-b]benzothiazine S,S-dioxide analogs

ARTHUR BARAZARTE, JOSE´ CAMACHO,AJOSE DOMıNGUEZ, GRICELA LOBO, NEIRA GAMBOA, JUAN RODRIGUES, MARIO V. CAPPARELLI, A NGEL A LVAREZ-LARENA, SEBASTIAN ANDUJAR, DANIEL ENRIZ AND JAIME CHARRISA

BIOORGANIC & MEDICINAL CHEMISTRY.

Elsevier

Año: 2008 vol. 16 p. 3661 - 3674

0968-0896

An improved procedure for the synthesis of 3-amino-9-arylsubstituted-thieno[3,2-b]benzothiazine S,S-dioxide 2-decarboxylatedis reported. Thieno-[3,2-b]benzothiazine S,S-dioxide derivatives were investigated for their abilities to inhibit b-hematinformation, hemoglobin hydrolysis and in vivo for their efficacy in rodent Plasmodium berghei. Compounds 5j–o were the most promisingas inhibitors of hemoglobin hydrolysis, however, the compounds are not as efficient as chloroquine. A structure–activity relationship(SAR) study was carried out in this series. Our results allow us to determine the minimal structural requirements to producethe biological response.