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

An improved procedure for the synthesis of 3-amino-9-arylsubstituted-thieno[3,2-b]benzothiazine S,S-dioxide 2-decarboxylated is reported. A conformational and electronic study on the most representative compounds of this series was carried out using ab initio calculations. A comparative study between thieno-[2,3-b]benzothiazine S,S-dioxide and thieno-[3,2-b]quinolones analogs could explain the different chemical behavior obtained for these compounds. Thieno-[3,2-b]benzothiazine S,S-dioxide derivatives were investigated for their abilities to inhibit β-hematin formation, hemoglobin hydrolysis and in vivo for their efficacy in rodent Plasmodium berghei.