title: Facile synthesis of the CERT inhibitor HPA-12 and some novel derivatives.
abstract: HPA-12 is an inhibitor of CERT-mediated non-vesicular transport of ceramide from the ER membranes to the Golgi apparatus. The inhibitor effectively blocks the synthesis of the membrane lipid sphingomyelin and may represent a novel drug prototype. Previous syntheses relied on non-commercial catalysts or specialized chemistries. Here we present a straightforward and effective method to synthesize HPA-12 from commercially available protected L-serinol in four steps. Some new analogues were synthesized and evaluated for their CERT-binding activity.
authors.affiliation: Institute for Chemistry, Humboldt Universität zu Berlin, Brook-Taylor-Str. 2, 12489 Berlin (Germany), Fax: (+49) 30-2093 6947; Chemistry Department, Faculty of Science, Suez Canal University, Ismailia (Egypt).
authors.forename: Essa M
authors.initials: EM
authors.lastname: Saied
authors.forename: Stephanie
authors.initials: S
authors.lastname: Diederich
authors.forename: Christoph
authors.initials: C
authors.lastname: Arenz
mesh_terms: D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; C441643:N-(3-hydroxy-1-hydroxymethyl-3-phenylpropyl)dodecanamide
keywords: binding assays; chiral pool; inhibitors; lipid trafficking; sphingolipids