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. Thieno-[3,2-b]benzothiazine S,S-dioxide derivatives were investigated for their abilities to inhibit beta-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.
Barazarte
Arthur
A
Laboratorio de Síntesis Orgánica, Universidad Central de Venezuela, Apartado 47206, Los Chaguaramos, 1041-A Caracas, Venezuela.
Camacho
José
J
Domínguez
José
J
Lobo
Gricela
G
Gamboa
Neira
N
Rodrigues
Juan
J
Capparelli
Mario V
MV
Alvarez-Larena
Angel
A
Andujar
Sebastian
S
Enriz
Daniel
D
Charris
Jaime
J
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001554:Benzene / Q000737:chemistry*; D018360:Crystallography, X-Ray; D005914:Globins / Q000378:metabolism; D006420:Hemeproteins / Q000096:biosynthesis; D051379:Mice; D008958:Models, Molecular; D015394:Molecular Structure; D010087:Oxides / Q000737:chemistry*; D010962:Plasmodium berghei / Q000187:drug effects; D055672:Static Electricity; D013329:Structure-Activity Relationship; D013843:Thiazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
D000962:Antimalarials; D006420:Hemeproteins; D010087:Oxides; D013843:Thiazines; C020753:hemozoin; D005914:Globins; D001554:Benzene