Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 52, Issue 20, Pages 6494-6498Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm900707n
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Funding
- NIH [R37-DK27083]
- W. M. Keck Foundation
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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.
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