Marcfortine and Paraherquamide Class of Anthelmintics: Discovery of PNU- 141962

Author(s): Byung H. Lee , Michael F. Clothier , Fred E. Dutton , Stephen J. Nelson , Sandra S. Johnson , David P. Thompson , Timothy G. Geary , Howard D. Whaley , Christopher L. Haber , Vincent P. Marshall , Gabe I. Kornis , Patty L. McNally , Joyce I. Ciadella , David G. Martin , Jerry W. Bowman , Carol A. Baker , Eileen M. Coscarelli , Susan J. Alexander-Bowman , John P. Davis , Erich W. Zinser , Veronica Wiley , Michael F. Lipton , Michael A. Mauragis .

Journal Name: Current Topics in Medicinal Chemistry

Volume 2 , Issue 7 , 2002

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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 fivemembered 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.

Keywords: anthelmintic, marcfortine, paraherquamide, pnu-141962, nematocide

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Article Details

Year: 2002
Page: [779 - 793]
Pages: 15
DOI: 10.2174/1568026023393705
Price: $58

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