title: Piperazinyl pyrimidine derivatives as potent gamma-secretase modulators.
abstract: The development of a novel series of piperazinyl pyrimidines as gamma-secretase modulators for potential use in the treatment of Alzheimer's disease is disclosed herein. Optimization of a screening hit provided a series of potent gamma-secretase modulators with >180-fold in vitro selectivity over inhibition of Notch cleavage.
authors.affiliation: Department of Drug Design and Optimization, Merck Research Laboratories, 33 Avenue Louis Pasteur, Boston, MA 02115, USA. alexey_rivkin@merck.com
authors.forename: Alexey
authors.initials: A
authors.lastname: Rivkin
authors.forename: Sean P
authors.initials: SP
authors.lastname: Ahearn
authors.forename: Stephanie M
authors.initials: SM
authors.lastname: Chichetti
authors.forename: Yoona R
authors.initials: YR
authors.lastname: Kim
authors.forename: Chaomin
authors.initials: C
authors.lastname: Li
authors.forename: Andrew
authors.initials: A
authors.lastname: Rosenau
authors.forename: Sam D
authors.initials: SD
authors.lastname: Kattar
authors.forename: Joon
authors.initials: J
authors.lastname: Jung
authors.forename: Sanjiv
authors.initials: S
authors.lastname: Shah
authors.forename: Bethany L
authors.initials: BL
authors.lastname: Hughes
authors.forename: Jamie L
authors.initials: JL
authors.lastname: Crispino
authors.forename: Richard E
authors.initials: RE
authors.lastname: Middleton
authors.forename: Alexander A
authors.initials: AA
authors.lastname: Szewczak
authors.forename: Benito
authors.initials: B
authors.lastname: Munoz
authors.forename: Mark S
authors.initials: MS
authors.lastname: Shearman
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016229:Amyloid beta-Peptides / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology; D045744:Cell Line, Tumor; D006367:HeLa Cells; D006801:Humans; D010446:Peptide Fragments / Q000037:antagonists & inhibitors / Q000378:metabolism; D010879:Piperazines / Q000737:chemistry* / Q000494:pharmacology; D011743:Pyrimidines / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; D010879:Piperazines; D011743:Pyrimidines; C538897:amyloid beta-protein (40-42); D053829:Amyloid Precursor Protein Secretases