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Curr Top Med Chem ; 2(7): 779-93, 2002 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-12052190

RESUMEN

Three distinct chemical classes for the control of gastrointestinal nematodes are available: benzimidazoles, imidazothiazoles, and macrocyclic lactones. The relentless development of drug resistance has severely limited the usefulness of such drugs and the search for a new class of compounds preferably with a different mode of action is an important endeavor. Marcfortine A (1), a metabolite of Penicillium roqueforti, is structurally related to paraherquamide A (2), originally isolated from Penicillium paraherquei. Chemically the two compounds differ only in one ring; in marcfortine A, ring G is six-membered and carries no substituents, while in paraherquamide A, ring G is five-membered with methyl and hydroxyl substituents at C14. Paraherquamide A (2) is superior to marcfortine A as a nematocide. 2-Desoxoparaherquamide A (PNU-141962, 53) has excellent nematocidal activity, a superior safely profile, and is the first semi-synthetic member of this totally new class of nematocides that is a legitimate candidate for development. This review describes the chemistry, efficacy and mode of action of PNU-141962.


Asunto(s)
Antihelmínticos/síntesis química , Indolizinas/síntesis química , Compuestos de Espiro/síntesis química , Animales , Antihelmínticos/química , Antihelmínticos/uso terapéutico , Humanos , Indolizinas/química , Indolizinas/uso terapéutico , Estructura Molecular , Infecciones por Nematodos/tratamiento farmacológico , Infecciones por Nematodos/prevención & control , Infecciones por Nematodos/veterinaria , Compuestos de Espiro/química , Compuestos de Espiro/uso terapéutico , Relación Estructura-Actividad
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