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

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

Title2-Oxo-tetrahydro-1,8-naphthyridines as selective inhibitors of malarial protein farnesyltransferase and as anti-malarials.
Publication TypeJournal Article
Year of Publication2008
AuthorsOlepu, S, Suryadevara, PK, Rivas, K, Yokoyama, K, Verlinde, CLMJ, Chakrabarti, D, Van Voorhis, WC, Gelb, MH
JournalBioorg Med Chem Lett
Volume18
Issue2
Pagination494-7
Date Published2008 Jan 15
ISSN1464-3405
KeywordsAlkyl and Aryl Transferases, Animals, Antimalarials, Drug Design, Enzyme Inhibitors, Naphthyridines, Plasmodium falciparum, Rats
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.
DOI10.1016/j.bmcl.2007.11.104
Alternate JournalBioorg. Med. Chem. Lett.
PubMed ID18077162