title: Tetracyclic sulfones as potent gamma-secretase inhibitors: synthesis and structure-activity relationship studies.
abstract: Complex tetracyclic sulfones were designed as gamma-secretase inhibitors and a stereoselective synthesis was achieved. Gamma-secretase activity was seen predominately in the (-) enantiomeric series. Compounds such as 2a and 2b showed remarkable in vitro and in vivo potency.
authors.affiliation: Merck Research Laboratories, Kenilworth, NJ 07033, USA. sasikumartk@yahoo.com
authors.forename: T K
authors.initials: TK
authors.lastname: Sasikumar
authors.forename: Duane A
authors.initials: DA
authors.lastname: Burnett
authors.forename: Theodros
authors.initials: T
authors.lastname: Asberom
authors.forename: Wen-Lian
authors.initials: WL
authors.lastname: Wu
authors.forename: Chad
authors.initials: C
authors.lastname: Bennett
authors.forename: David
authors.initials: D
authors.lastname: Cole
authors.forename: Ruo
authors.initials: R
authors.lastname: Xu
authors.forename: William J
authors.initials: WJ
authors.lastname: Greenlee
authors.forename: John
authors.initials: J
authors.lastname: Clader
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.forename: Lynn
authors.initials: L
authors.lastname: Hyde
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors; D000818:Animals; D015195:Drug Design; D022781:Hepatocytes / Q000378:metabolism; D006801:Humans; D051379:Mice; D011480:Protease Inhibitors / Q000138:chemical synthesis*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D011480:Protease Inhibitors; D013450:Sulfones; D053829:Amyloid Precursor Protein Secretases