EXTRAORDINARILY POTENT ANTIMALARIAL COMPOUNDS - NEW, STRUCTURALLY SIMPLE, EASILY SYNTHESIZED, TRICYCLIC 1,2,4-TRIOXANES

被引：100

作者：

POSNER, GH ^{[1
]}

OH, CH ^{[1
]}

GERENA, L ^{[1
]}

MILHOUS, WK ^{[1
]}

机构：

[1] WALTER REED ARMY MED CTR,DIV EXPTL THERAPEUT,WASHINGTON,DC 20307

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 1992年 / 35卷 / 13期

关键词：

D O I：

10.1021/jm00091a014

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

New, racemic, tricyclic trioxane alcohol 3 was designed and synthesized as a structurally simple analog of clinically useful, tetracyclic, antimalarial artemisinin. A series of 20 ester and ether derivatives of alcohol 3 were prepared easily, without destruction of the essential trioxane system. Chemical structure-antimalarial activity for each derivative was evaluated in vitro against chloroquine-resistant and chloroquine-sensitive Plasmodium falciparum parasites. Many of these derivatives were highly efficacious; carboxylate ester 9f, carbamate ester 10a, and sulfonate ester 12a had antimalarial potency similar to that of artemisinin, and carboxylate esters 9b and 9d, carbamate esters 10b and 10c, and phosphate esters 11a-c had antimalarial potency up to 7 times higher than that of artemisinin. Several of these most active analogs (e.g., carboxylate 9b and carbamates 10a and 10c) are stable crystalline solids, a feature of considerable practical value for any new drug candidate.

引用

页码：2459 / 2467

页数：9

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