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Extraordinarily potent antimalarial compounds: new, structurally simple, easily synthesized, tricyclic 1,2,4-trioxanes.

Abstract：

: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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Posner GH,Oh CH,Gerena L,Milhous WK

doi

10.1021/jm00091a014

keywords:

subject

Has Abstract

pub_date

1992-06-26 00:00:00

pages

2459-67

issue

13

eissn

0022-2623

issn

1520-4804

journal_volume

35

pub_type

杂志文章

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