title: Quinolizidinone carboxylic acids as CNS penetrant, selective m1 allosteric muscarinic receptor modulators.
abstract: Positive allosteric modulation of the M1 muscarinic receptor represents an approach to treat the cognitive decline in patients with Alzheimer's disease. Replacement of a quinolone ring system in a quinolone carboxylic acid series of M1 modulators with a quinolizidinone bearing a basic amine linkage led to a series of compounds with higher free fraction, enhanced CNS exposure, and improved efficacy in rodent in vivo models of cognition.
authors.affiliation: Departments of Medicinal Chemistry.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Kuduk
authors.affiliation: Departments of Medicinal Chemistry.
authors.forename: Ronald K
authors.initials: RK
authors.lastname: Chang
authors.affiliation: Departments of Medicinal Chemistry.
authors.forename: Christina N
authors.initials: CN
authors.lastname: Di Marco
authors.affiliation: Alzheimer's Research.
authors.forename: William J
authors.initials: WJ
authors.lastname: Ray
authors.affiliation: Alzheimer's Research.
authors.forename: Lei
authors.initials: L
authors.lastname: Ma
authors.affiliation: Alzheimer's Research.
authors.forename: Marion
authors.initials: M
authors.lastname: Wittmann
authors.affiliation: Alzheimer's Research.
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Seager
authors.affiliation: Drug Metabolism.
authors.forename: Kenneth A
authors.initials: KA
authors.lastname: Koeplinger
authors.affiliation: Drug Metabolism.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Thompson
authors.affiliation: Departments of Medicinal Chemistry.
authors.forename: George D
authors.initials: GD
authors.lastname: Hartman
authors.affiliation: Departments of Medicinal Chemistry.
authors.forename: Mark T
authors.initials: MT
authors.lastname: Bilodeau
keywords: Alzheimer’s; M1 muscarinic receptor; Quinolizidinone; allosteric modulator; cognition