title: Part 2. Notch-sparing γ-secretase inhibitors: The study of novel γ-amino naphthyl alcohols.
abstract: One therapeutic approach for Alzheimer's disease is to inhibit the cleavage of the amyloid precursor protein (APP) by γ-secretase. At the beginning of a series of studies from our laboratories, a series of novel γ-amino alcohols (1) were found to possess γ-secretase inhibitory activity and Notch-sparing effects. A new one-pot synthesis of γ-amino alcohols and the structure-activity relationship (SAR) of these analogs will be discussed.
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: 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: Vivien
authors.initials: V
authors.lastname: Sun
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: 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: Pamela
authors.initials: P
authors.lastname: Osenkowski
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: Wenjuan
authors.initials: W
authors.lastname: Ye
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: D000605:Amino Alcohols / Q000138:chemical synthesis / Q000494:pharmacology; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors; D000818:Animals; D006801:Humans; D008862:Microsomes, Liver / Q000378:metabolism; D009281:Naphthalenes / Q000138:chemical synthesis / Q000494:pharmacology; D010446:Peptide Fragments / Q000037:antagonists & inhibitors; D011412:Propanolamines / Q000138:chemical synthesis / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D051381:Rats; D051881:Receptor, Notch1 / Q000378:metabolism*; D013329:Structure-Activity Relationship
chemical_list: D000605:Amino Alcohols; D016229:Amyloid beta-Peptides; C497761:NOTCH1 protein, human; D009281:Naphthalenes; C497763:Notch1 protein, rat; D010446:Peptide Fragments; D011412:Propanolamines; D011480:Protease Inhibitors; D051881:Receptor, Notch1; C000621216:ZM39923; C075222:amyloid beta-protein (1-42); D053829:Amyloid Precursor Protein Secretases
keywords: Alzheimer’s disease; Aβ production; Notch-processing; γ-Amino alcohols; γ-Secretase inhibitors