title: 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.
authors: Department of Chemistry, University of Washington, Seattle, WA 98195, USA.
authors: Srinivas
authors: S
authors: Olepu
authors: Praveen Kumar
authors: PK
authors: Suryadevara
authors: Kasey
authors: K
authors: Rivas
authors: Kohei
authors: K
authors: Yokoyama
authors: Christophe L M J
authors: CL
authors: Verlinde
authors: Debopam
authors: D
authors: Chakrabarti
authors: Wesley C
authors: WC
authors: Van Voorhis
authors: Michael H
authors: MH
authors: Gelb
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors*; D000818:Animals; D000962:Antimalarials / Q000493:pharmacokinetics / Q000494:pharmacology*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000493:pharmacokinetics / Q000494:pharmacology*; D009287:Naphthyridines / Q000493:pharmacokinetics / Q000494:pharmacology*; D010963:Plasmodium falciparum / Q000187:drug effects; D051381:Rats
chemical_list: D000962:Antimalarials; D004791:Enzyme Inhibitors; D009287:Naphthyridines; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase