title: Design and synthesis of an aminopiperidine series of γ-secretase modulators.
abstract: The design, synthesis, and SAR of cyclic diamines as novel γ secretase modulators (GSMs) are presented in this Letter. Starting from information in the literature and in-house cyclic diamines library, we have found a 3(S)-aminopiperidine as a potent structure for lowering Aβ42 production both in vitro and in vivo.
authors.affiliation: Dainippon Sumitomo Pharma Co., Ltd, Kasugade Naka 3-1-98, Konohana-ku, Osaka 554-0022, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Dainippon Sumitomo Pharma Co., Ltd, Enoki 33-94, Suita, Osaka 564-0053, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Iwama
authors.affiliation: Dainippon Sumitomo Pharma Co., Ltd, Enoki 33-94, Suita, Osaka 564-0053, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Fusano
authors.affiliation: Dainippon Sumitomo Pharma Co., Ltd, Enoki 33-94, Suita, Osaka 564-0053, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Kato
authors.affiliation: Dainippon Sumitomo Pharma Co., Ltd, Enoki 33-94, Suita, Osaka 564-0053, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ikeda
authors.affiliation: Dainippon Sumitomo Pharma Co., Ltd, Enoki 33-94, Suita, Osaka 564-0053, Japan.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Teranishi
authors.affiliation: Dainippon Sumitomo Pharma Co., Ltd, Enoki 33-94, Suita, Osaka 564-0053, Japan.
authors.forename: Akemi
authors.initials: A
authors.lastname: Nishihara
authors.affiliation: Dainippon Sumitomo Pharma Co., Ltd, Enoki 33-94, Suita, Osaka 564-0053, Japan. Electronic address: masanori-tobe@ds-pharma.co.jp.
authors.forename: Masanori
authors.initials: M
authors.lastname: Tobe
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010880:Piperidines; C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer’s disease; Amyloid β peptide; Piperidine; γ-Secretase inhibitor; γ-Secretase modulator