title: Discovery of fused 5,6-bicyclic heterocycles as γ-secretase modulators.
abstract: We herein report the discovery of four series of fused 5,6-bicyclic heterocycles as γ-secretase modulators. Synthesis and SAR of these series are discussed. These compounds represent a new class of γ-secretase modulators that demonstrate moderate to good in vitro potency in inhibiting Aβ(42) production.
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. jun.qin@merck.com
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
authors.forename: Pawan
authors.initials: P
authors.lastname: Dhondi
authors.forename: Xianhai
authors.initials: X
authors.lastname: Huang
authors.forename: Mihirbaran
authors.initials: M
authors.lastname: Mandal
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Dmitri
authors.initials: D
authors.lastname: Pissarnitski
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.forename: Robert
authors.initials: R
authors.lastname: Aslanian
authors.forename: Zhaoning
authors.initials: Z
authors.lastname: Zhu
authors.forename: William
authors.initials: W
authors.lastname: Greenlee
authors.forename: John
authors.initials: J
authors.lastname: Clader
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
authors.forename: Mary
authors.initials: M
authors.lastname: Cohen-Williams
authors.forename: Nicholas
authors.initials: N
authors.lastname: Jones
authors.forename: Lynn
authors.initials: L
authors.lastname: Hyde
authors.forename: Anandan
authors.initials: A
authors.lastname: Palani
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy; D053829:Amyloid Precursor Protein Secretases / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D006801:Humans; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D016229:Amyloid beta-Peptides; D019086:Bridged Bicyclo Compounds, Heterocyclic; D053829:Amyloid Precursor Protein Secretases