Investigation of N-aryl-3-alkylidenepyrrolinones as potential Niemann-Pick type C disease therapeutics.
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ABSTRACT:
SUBMITTER: Cosner CC
PROVIDER: S-EPMC2791921 | biostudies-literature | 2009 Oct
REPOSITORIES: biostudies-literature
Publications
Investigation of N-aryl-3-alkylidenepyrrolinones as potential Niemann-Pick type C disease therapeutics.
Cosner Casey C CC Markiewicz John T JT Bourbon Pauline P Mariani Christopher J CJ Wiest Olaf O Rujoi Madalina M Rosenbaum Anton I AI Huang Amy Y AY Maxfield Frederick R FR Helquist Paul P
Journal of medicinal chemistry 20091001 20
A five-step synthesis of an array of N-aryl-3-alkylidenepyrrolinones, which are potential Niemann-Pick type C (NPC) disease therapeutics, is described. The synthetic route allows for the production of analogues, including photoaffinity and biotinylated derivatives. Compound 1a increased esterification by acyl-coenzyme A:cholesteryl acyltransferase in NPC1 mutant cells. It also decreased LDL uptake and increased cholesterol efflux in both NPC1-deficient and normal cells. ...[more]
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