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

被引：30

作者：

Barazarte, Arthur ^{[1
]}

Camacho, Jose ^{[1
]}

Dominguez, Jose ^{[1
]}

Lobo, Gricela ^{[1
]}

Gamboa, Neira ^{[2
]}

Rodrigues, Juan ^{[2
]}

Capparelli, Mario V. ^{[3
]}

Alvarez-Larena, Angel ^{[4
]}

Andujar, Sebastian

Enriz, Daniel

Charris, Jaime ^{[1
]}

机构：

[1] Cent Univ Venezuela, Lab Sint Organ, Caracas, Venezuela

[2] Cent Univ Venezuela, Fac Farm, Unidad Bioquim, Caracas, Venezuela

[3] Cent Univ Venezuela, Fac Farm, Escuela Quim, Caracas, Venezuela

[4] Univ Autonoma Barcelona, Serv Difracc Rayos X, Bellaterra, Spain

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2008年 / 16卷 / 07期

关键词：

thieno; 1,4-benzothiazines; cyclization; antimalarial; SAR study;

D O I：

10.1016/j.bmc.2008.02.011

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：3661 / 3674

页数：14

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