title: Synthesis, antimalarial activity, structure-activity relationship analysis of thieno-[3,2-b]benzothiazine S,S-dioxide analogs.
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 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.
authors.affiliation: Laboratorio de Síntesis Orgánica, Universidad Central de Venezuela, Apartado 47206, Los Chaguaramos, 1041-A Caracas, Venezuela.
authors.forename: Arthur
authors.initials: A
authors.lastname: Barazarte
authors.forename: José
authors.initials: J
authors.lastname: Camacho
authors.forename: José
authors.initials: J
authors.lastname: Domínguez
authors.forename: Gricela
authors.initials: G
authors.lastname: Lobo
authors.forename: Neira
authors.initials: N
authors.lastname: Gamboa
authors.forename: Juan
authors.initials: J
authors.lastname: Rodrigues
authors.forename: Mario V
authors.initials: MV
authors.lastname: Capparelli
authors.forename: Angel
authors.initials: A
authors.lastname: Alvarez-Larena
authors.forename: Sebastian
authors.initials: S
authors.lastname: Andujar
authors.forename: Daniel
authors.initials: D
authors.lastname: Enriz
authors.forename: Jaime
authors.initials: J
authors.lastname: Charris
mesh_terms: 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*
chemical_list: D000962:Antimalarials; D006420:Hemeproteins; D010087:Oxides; D013843:Thiazines; C020753:hemozoin; D005914:Globins; D001554:Benzene