title: Design and synthesis of benzoazepinone-derived cyclic malonamides and aminoamides as potent gamma-secretase inhibitors.
abstract: We report the synthesis of benzoazepine-derived cyclic malonamides (2) and aminoamides (3) as gamma-secretase inhibitors for the potential treatment of Alzheimer's disease. The in vitro structure-activity relationships of 2 and 3 along with dog pharmacokinetic results are described.
authors.affiliation: Bristol-Myers Squibb Co., Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA. michael.yang@bms.com
authors.forename: Michael G
authors.initials: MG
authors.lastname: Yang
authors.forename: Jian-Liang
authors.initials: JL
authors.lastname: Shi
authors.forename: Dilip P
authors.initials: DP
authors.lastname: Modi
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wells
authors.forename: Brian M
authors.initials: BM
authors.lastname: Cochran
authors.forename: Mark A
authors.initials: MA
authors.lastname: Wolf
authors.forename: Lorin A
authors.initials: LA
authors.lastname: Thompson
authors.forename: Mercy M
authors.initials: MM
authors.lastname: Ramanjulu
authors.forename: Arthur H
authors.initials: AH
authors.lastname: Roach
authors.forename: Robert
authors.initials: R
authors.lastname: Zaczek
authors.forename: David W
authors.initials: DW
authors.lastname: Robertson
authors.forename: Ruth R
authors.initials: RR
authors.lastname: Wexler
authors.forename: Richard E
authors.initials: RE
authors.lastname: Olson
mesh_terms: D000577:Amides / Q000494:pharmacology*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D001381:Azepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003500:Cyclization; D008958:Models, Molecular; D013329:Structure-Activity Relationship
chemical_list: D000577:Amides; D001381:Azepines; D053829:Amyloid Precursor Protein Secretases