title: Rational design of novel, potent piperazinone and imidazolidinone BACE1 inhibitors.
abstract: Guided by structure-based design, we synthesized two novel series of potent inhibitors of BACE1 and generated extensive SAR around both the prime and non-prime side binding pockets. The key feature of both series is a cyclic amine motif specifically crafted to achieve interactions with both the flap and with the S2' pocket.
authors.affiliation: Schering-Plough Research Institute, 2015 Galloping Hill Road, Kenilworth, NJ 07033, USA. jared.cumming@spcorp.com
authors.forename: J N
authors.initials: JN
authors.lastname: Cumming
authors.forename: T X
authors.initials: TX
authors.lastname: Le
authors.forename: S
authors.initials: S
authors.lastname: Babu
authors.forename: C
authors.initials: C
authors.lastname: Carroll
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.forename: L
authors.initials: L
authors.lastname: Favreau
authors.forename: P
authors.initials: P
authors.lastname: Gaspari
authors.forename: T
authors.initials: T
authors.lastname: Guo
authors.forename: D W
authors.initials: DW
authors.lastname: Hobbs
authors.forename: Y
authors.initials: Y
authors.lastname: Huang
authors.forename: U
authors.initials: U
authors.lastname: Iserloh
authors.forename: M E
authors.initials: ME
authors.lastname: Kennedy
authors.forename: R
authors.initials: R
authors.lastname: Kuvelkar
authors.forename: G
authors.initials: G
authors.lastname: Li
authors.forename: J
authors.initials: J
authors.lastname: Lowrie
authors.forename: N A
authors.initials: NA
authors.lastname: McHugh
authors.forename: L
authors.initials: L
authors.lastname: Ozgur
authors.forename: J
authors.initials: J
authors.lastname: Pan
authors.forename: E M
authors.initials: EM
authors.lastname: Parker
authors.forename: K
authors.initials: K
authors.lastname: Saionz
authors.forename: A W
authors.initials: AW
authors.lastname: Stamford
authors.forename: C
authors.initials: C
authors.lastname: Strickland
authors.forename: D
authors.initials: D
authors.lastname: Tadesse
authors.forename: J
authors.initials: J
authors.lastname: Voigt
authors.forename: L
authors.initials: L
authors.lastname: Wang
authors.forename: Y
authors.initials: Y
authors.lastname: Wu
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: Q
authors.initials: Q
authors.lastname: Zhang
mesh_terms: D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D018360:Crystallography, X-Ray; D004195:Disease Models, Animal; D015195:Drug Design; D006801:Humans; D048289:Imidazolidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D051379:Mice; D008822:Mice, Transgenic; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D048289:Imidazolidines; D010879:Piperazines; C004916:ethylene urea; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human