title: Part 3: Notch-sparing γ-secretase inhibitors: SAR studies of 2-substituted aminopyridopyrimidinones.
abstract: In search for novel lead compounds as γ-secretase inhibitors, analogs of aminopyrido[2,3-d]pyrimidin-7-ones (I) were synthesized and evaluated for inhibitory effects on amyloid-β-peptide production and cleavage of the Notch1 receptor mediated by γ-secretase. Selected pyridopyrimidines, such as 1, 8, 9, 10, 11 and 16 are γ-secretase inhibitors that did not have an effect on Notch1 receptor processing.
authors.affiliation: Laboratory for Experimental Alzheimer Drugs (LEAD), Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Harvard Institutes of Medicine, Boston, MA 02115, United States.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Laboratory for Experimental Alzheimer Drugs (LEAD), Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Harvard Institutes of Medicine, Boston, MA 02115, United States.
authors.forename: Dai
authors.initials: D
authors.lastname: Lu
authors.affiliation: Laboratory for Experimental Alzheimer Drugs (LEAD), Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Harvard Institutes of Medicine, Boston, MA 02115, United States.
authors.forename: Han-Xun
authors.initials: HX
authors.lastname: Wei
authors.affiliation: Laboratory for Experimental Alzheimer Drugs (LEAD), Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Harvard Institutes of Medicine, Boston, MA 02115, United States.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Gu
authors.affiliation: Laboratory for Experimental Alzheimer Drugs (LEAD), Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Harvard Institutes of Medicine, Boston, MA 02115, United States.
authors.forename: Dennis J
authors.initials: DJ
authors.lastname: Selkoe
authors.affiliation: Laboratory for Experimental Alzheimer Drugs (LEAD), Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Harvard Institutes of Medicine, Boston, MA 02115, United States.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Wolfe
authors.affiliation: Laboratory for Experimental Alzheimer Drugs (LEAD), Center for Neurologic Diseases, Harvard Medical School and Brigham and Women's Hospital, 77 Avenue Louis Pasteur, Harvard Institutes of Medicine, Boston, MA 02115, United States. Electronic address: caugelli-szafran@southernresearch.org.
authors.forename: Corinne E
authors.initials: CE
authors.lastname: Augelli-Szafran
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors; D000818:Animals; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D010446:Peptide Fragments / Q000037:antagonists & inhibitors; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D011728:Pyridones / Q000138:chemical synthesis / Q000494:pharmacology*; D011743:Pyrimidines / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D051881:Receptor, Notch1 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D016229:Amyloid beta-Peptides; C497761:NOTCH1 protein, human; C497763:Notch1 protein, rat; D010446:Peptide Fragments; D011480:Protease Inhibitors; D011728:Pyridones; D011743:Pyrimidines; D051881:Receptor, Notch1; C078592:amyloid beta-protein (1-40); D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer’s disease; Aminopyridopyrimidines; Aβ production; Notch-processing; γ-Secretase inhibitors