title: Synthesis and Evaluation of 5-Fluoro-2-aryloxazolo[5,4-b]pyridines as β-Amyloid PET Ligands and Identification of MK-3328.
abstract: 5-Fluoro-2-aryloxazolo[5,4-b]pyridines were synthesized and investigated as potential (18)F containing β-amyloid PET ligands. In competition binding assays using human AD brain homogenates, compounds 14b, 16b, and 17b were identified as having favorable potency versus human β-amyloid plaque and were radiolabeled for further evaluation in in vitro binding and in vivo PET imaging experiments. These studies led to the identification of 17b (MK-3328) as a candidate PET ligand for the clinical assessment of β-amyloid plaque load.
authors.affiliation: Departments of Medicinal Chemistry, Imaging, and Chemical Modeling and Informatics, Merck Research Laboratories, Merck & Co., Inc. , P.O. Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Scott T
authors.initials: ST
authors.lastname: Harrison
authors.affiliation: Departments of Medicinal Chemistry, Imaging, and Chemical Modeling and Informatics, Merck Research Laboratories, Merck & Co., Inc. , P.O. Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: James
authors.initials: J
authors.lastname: Mulhearn
authors.affiliation: Departments of Medicinal Chemistry, Imaging, and Chemical Modeling and Informatics, Merck Research Laboratories, Merck & Co., Inc. , P.O. Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Scott E
authors.initials: SE
authors.lastname: Wolkenberg
authors.affiliation: Departments of Medicinal Chemistry, Imaging, and Chemical Modeling and Informatics, Merck Research Laboratories, Merck & Co., Inc. , P.O. Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: Miller
authors.affiliation: Departments of Medicinal Chemistry, Imaging, and Chemical Modeling and Informatics, Merck Research Laboratories, Merck & Co., Inc. , P.O. Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Stacey S
authors.initials: SS
authors.lastname: O'Malley
authors.affiliation: Departments of Medicinal Chemistry, Imaging, and Chemical Modeling and Informatics, Merck Research Laboratories, Merck & Co., Inc. , P.O. Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Zhizhen
authors.initials: Z
authors.lastname: Zeng
authors.affiliation: Departments of Medicinal Chemistry, Imaging, and Chemical Modeling and Informatics, Merck Research Laboratories, Merck & Co., Inc. , P.O. Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: David L
authors.initials: DL
authors.lastname: Williams
authors.affiliation: Departments of Medicinal Chemistry, Imaging, and Chemical Modeling and Informatics, Merck Research Laboratories, Merck & Co., Inc. , P.O. Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Eric D
authors.initials: ED
authors.lastname: Hostetler
authors.affiliation: Departments of Medicinal Chemistry, Imaging, and Chemical Modeling and Informatics, Merck Research Laboratories, Merck & Co., Inc. , P.O. Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Sandra
authors.initials: S
authors.lastname: Sanabria-Bohórquez
authors.affiliation: Departments of Medicinal Chemistry, Imaging, and Chemical Modeling and Informatics, Merck Research Laboratories, Merck & Co., Inc. , P.O. Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Linda
authors.initials: L
authors.lastname: Gammage
authors.affiliation: Departments of Medicinal Chemistry, Imaging, and Chemical Modeling and Informatics, Merck Research Laboratories, Merck & Co., Inc. , P.O. Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Hong
authors.initials: H
authors.lastname: Fan
authors.affiliation: Departments of Medicinal Chemistry, Imaging, and Chemical Modeling and Informatics, Merck Research Laboratories, Merck & Co., Inc. , P.O. Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Cyrille
authors.initials: C
authors.lastname: Sur
authors.affiliation: Departments of Medicinal Chemistry, Imaging, and Chemical Modeling and Informatics, Merck Research Laboratories, Merck & Co., Inc. , P.O. Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: J Christopher
authors.initials: JC
authors.lastname: Culberson
authors.affiliation: Departments of Medicinal Chemistry, Imaging, and Chemical Modeling and Informatics, Merck Research Laboratories, Merck & Co., Inc. , P.O. Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Hargreaves
authors.affiliation: Departments of Medicinal Chemistry, Imaging, and Chemical Modeling and Informatics, Merck Research Laboratories, Merck & Co., Inc. , P.O. Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: Jacquelynn J
authors.initials: JJ
authors.lastname: Cook
authors.affiliation: Departments of Medicinal Chemistry, Imaging, and Chemical Modeling and Informatics, Merck Research Laboratories, Merck & Co., Inc. , P.O. Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: George D
authors.initials: GD
authors.lastname: Hartman
authors.affiliation: Departments of Medicinal Chemistry, Imaging, and Chemical Modeling and Informatics, Merck Research Laboratories, Merck & Co., Inc. , P.O. Box 4, West Point, Pennsylvania 19486, United States.
authors.forename: James C
authors.initials: JC
authors.lastname: Barrow
keywords: Alzheimer’s disease; PET; fluorine-18; oxazolo[5,4-b]pyridine; positron emission tomography; β-amyloid plaque