title: Discovery of a Potent Pyrazolopyridine Series of γ-Secretase Modulators.
abstract: The synthesis and structure-activity relationship of a novel series of pyrazolopyridines are reported. These compounds represent a new class of γ-secretase modulators that demonstrate good in vitro potency in inhibiting Aβ42 production. Examples with statistically significant in vivo efficacy in reducing the production of rat cerebrospinal fluid Aβ42 were also identified.
authors.affiliation: Department of Medicinal Chemistry and Neurodegenerative Diseases, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
authors.forename: Jun
authors.initials: J
authors.lastname: Qin
authors.affiliation: Department of Medicinal Chemistry and Neurodegenerative Diseases, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
authors.forename: Wei
authors.initials: W
authors.lastname: Zhou
authors.affiliation: Department of Medicinal Chemistry and Neurodegenerative Diseases, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
authors.forename: Xianhai
authors.initials: X
authors.lastname: Huang
authors.affiliation: Department of Medicinal Chemistry and Neurodegenerative Diseases, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
authors.forename: Pawan
authors.initials: P
authors.lastname: Dhondi
authors.affiliation: Department of Medicinal Chemistry and Neurodegenerative Diseases, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
authors.forename: Anandan
authors.initials: A
authors.lastname: Palani
authors.affiliation: Department of Medicinal Chemistry and Neurodegenerative Diseases, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Aslanian
authors.affiliation: Department of Medicinal Chemistry and Neurodegenerative Diseases, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
authors.forename: Zhaoning
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: Department of Medicinal Chemistry, Merck Research Laboratories , 126 East Lincoln Avenue, Rahway, New Jersey 07065, United States.
authors.forename: William
authors.initials: W
authors.lastname: Greenlee
authors.affiliation: Department of Medicinal Chemistry and Neurodegenerative Diseases, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
authors.forename: Mary
authors.initials: M
authors.lastname: Cohen-Williams
authors.affiliation: Department of Medicinal Chemistry and Neurodegenerative Diseases, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Jones
authors.affiliation: Department of Medicinal Chemistry and Neurodegenerative Diseases, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
authors.forename: Lynn
authors.initials: L
authors.lastname: Hyde
authors.affiliation: Department of Medicinal Chemistry and Neurodegenerative Diseases, Merck Research Laboratories , 2015 Galloping Hill Road, Kenilworth, New Jersey 07033, United States.
authors.forename: Lili
authors.initials: L
authors.lastname: Zhang
keywords: Alzheimer's disease; Notch; amyloid-β peptide; γ-secretase modulator