Document Report Card

ID: ALA1155241

Journal: J Med Chem

Title: Investigation of N-aryl-3-alkylidenepyrrolinones as potential Niemann-Pick type C disease therapeutics.

Authors: Cosner CC, Markiewicz JT, Bourbon P, Mariani CJ, Wiest O, Rujoi M, Rosenbaum AI, Huang AY, Maxfield FR, Helquist P.

Abstract: 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.

CiteXplore: 19772346

DOI: 10.1021/jm900707n