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2-Oxo-tetrahydro-1,8-naphthyridines as selective inhibitors of malarial protein farnesyltransferase and as anti-malarials.

ABSTRACT: A new class of 2-oxo-tetrahydro-1,8-naphthyridine-based protein farnesyltransferase inhibitors were synthesized and found to inhibit protein farnesyltransferase from the malaria parasite with potencies in the low nanomolar range. The compounds were much less potent on mammalian protein prenyltransferases. Two of the compounds block the growth of malaria in culture with potencies in the sub-micromolar range. Some of the compounds were found to be much more metabolically stable than previously described tetrahydroquinoline-based protein farnesyltransferase inhibitors.

SUBMITTER: Olepu S

PROVIDER: S-EPMC2275803 | biostudies-literature | 2008 Jan

REPOSITORIES: biostudies-literature

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2-Oxo-tetrahydro-1,8-naphthyridines as selective inhibitors of malarial protein farnesyltransferase and as anti-malarials.

Olepu Srinivas S Suryadevara Praveen Kumar PK Rivas Kasey K Yokoyama Kohei K Verlinde Christophe L M J CL Chakrabarti Debopam D Van Voorhis Wesley C WC Gelb Michael H MH

Bioorganic & medicinal chemistry letters 20071203 2

A new class of 2-oxo-tetrahydro-1,8-naphthyridine-based protein farnesyltransferase inhibitors were synthesized and found to inhibit protein farnesyltransferase from the malaria parasite with potencies in the low nanomolar range. The compounds were much less potent on mammalian protein prenyltransferases. Two of the compounds block the growth of malaria in culture with potencies in the sub-micromolar range. Some of the compounds were found to be much more metabolically stable than previously des ...[more]

PMID: 18077162

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