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

A. BARAZARTE, J. CAMACHO, J. DOMÍNGUEZ, G. LOBO, N. GAMBOA, J. RODRIGUES, M. V. CAPPARELLI, A. ÁLVAREZ-LARENA, S. A. ANDUJAR, R.D.ENRIZ, J. CHARRIS.

BIOORGANIC & MEDICINAL CHEMISTRY.

Elsevier

Lugar: Amsterdam; Año: 2008 vol. 16 p. 3661 - 3674

0968-0896

Abstract—An improved procedure for the synthesis of 3-amino-9-arylsubstituted-thieno[3,2-b]benzothiazine S,S-dioxide 2-decarboxylated  is reported. Thieno-[3,2-b]benzothiazine S,S-dioxide derivatives were investigated for their abilities to inhibit b-hematin  formation, hemoglobin hydrolysis and in vivo for their efficacy in rodent Plasmodium berghei. Compounds 5j–o were the most promising  as 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 produce the biological response.