title: Synthesis and SAR study of tricyclic sulfones as γ-secretase inhibitors: C-6 and C-8 positions.
abstract: SAR exploration at C-6 and C-8 positions of the tricyclic sulfone series was carried out. Several functional groups were found to be well tolerated at C-6 and C-8 positions. Selective combination of C-6 and C-8 modification resulted in new tricyclic sulfone analogs with efficacy in in vivo mouse Aβ(40) lowering model.
authors.affiliation: Merck Research Laboratory, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. jing.su2@Merck.com
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.forename: Haiqun
authors.initials: H
authors.lastname: Tang
authors.forename: Brian A
authors.initials: BA
authors.lastname: McKittrick
authors.forename: Ruo
authors.initials: R
authors.lastname: Xu
authors.forename: John W
authors.initials: JW
authors.lastname: Clader
authors.forename: William J
authors.initials: WJ
authors.lastname: Greenlee
authors.forename: Lynn
authors.initials: L
authors.lastname: Hyde
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D003500:Cyclization; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D051379:Mice; D015394:Molecular Structure; D010446:Peptide Fragments / Q000378:metabolism; D013329:Structure-Activity Relationship; D013450:Sulfones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D004791:Enzyme Inhibitors; D010446:Peptide Fragments; D013450:Sulfones; C078592:amyloid beta-protein (1-40); D053829:Amyloid Precursor Protein Secretases