title: Potent pyrrolidine- and piperidine-based BACE-1 inhibitors.
abstract: Based on lead compound 1 identified from the patent literature, we developed novel patentable BACE-1 inhibitors by introducing a cyclic amine scaffold. Extensive SAR studies on both pyrrolidines and piperidines ultimately led to inhibitor 2f, one of the most potent inhibitors synthesized to date.
authors.affiliation: Department of Chemical Research, Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. ulrich.iserloh@spcorp.com
authors.forename: U
authors.initials: U
authors.lastname: Iserloh
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: J N
authors.initials: JN
authors.lastname: Cumming
authors.forename: J
authors.initials: J
authors.lastname: Pan
authors.forename: L Y
authors.initials: LY
authors.lastname: Wang
authors.forename: A W
authors.initials: AW
authors.lastname: Stamford
authors.forename: M E
authors.initials: ME
authors.lastname: Kennedy
authors.forename: R
authors.initials: R
authors.lastname: Kuvelkar
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: E M
authors.initials: EM
authors.lastname: Parker
authors.forename: C
authors.initials: C
authors.lastname: Strickland
authors.forename: J
authors.initials: J
authors.lastname: Voigt
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism; D002460:Cell Line; D018360:Crystallography, X-Ray; D006801:Humans; D006860:Hydrogen Bonding; D008958:Models, Molecular; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D010880:Piperidines; D011480:Protease Inhibitors; D011759:Pyrrolidines; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human