title: Investigation of N-aryl-3-alkylidenepyrrolinones as potential Niemann-Pick type C disease therapeutics.
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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Notre Dame, 250 Nieuwland Science Hall, Notre Dame, Indiana 46556, USA.
authors.forename: Casey C
authors.initials: CC
authors.lastname: Cosner
authors.forename: John T
authors.initials: JT
authors.lastname: Markiewicz
authors.forename: Pauline
authors.initials: P
authors.lastname: Bourbon
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Mariani
authors.forename: Olaf
authors.initials: O
authors.lastname: Wiest
authors.forename: Madalina
authors.initials: M
authors.lastname: Rujoi
authors.forename: Anton I
authors.initials: AI
authors.lastname: Rosenbaum
authors.forename: Amy Y
authors.initials: AY
authors.lastname: Huang
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Maxfield
authors.forename: Paul
authors.initials: P
authors.lastname: Helquist
mesh_terms: D000818:Animals; D016466:CHO Cells; D002784:Cholesterol / Q000378:metabolism; D006224:Cricetinae; D003412:Cricetulus; D006801:Humans; D052556:Niemann-Pick Disease, Type C / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D011758:Pyrroles; C013231:pyrroline; D002784:Cholesterol