title: Tricyclic sulfones as orally active gamma-secretase inhibitors: synthesis and structure-activity relationship studies.
abstract: Tricyclic sulfones were designed as gamma-secretase inhibitors and found to have excellent potency. Extensive SAR shows that a large number of sulfonamides at position 7 of the tricycle are very well tolerated. Compounds such as 15a and 15c showed remarkable 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: Li
authors.initials: L
authors.lastname: Qiang
authors.forename: Duane A
authors.initials: DA
authors.lastname: Burnett
authors.forename: David
authors.initials: D
authors.lastname: Cole
authors.forename: Ruo
authors.initials: R
authors.lastname: Xu
authors.forename: Hongmei
authors.initials: H
authors.lastname: Li
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: D000284:Administration, Oral; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000097:blood; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects; D051379:Mice; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013450:Sulfones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D016229:Amyloid beta-Peptides; D011480:Protease Inhibitors; D013449:Sulfonamides; D013450:Sulfones; D053829:Amyloid Precursor Protein Secretases