title: Design of potent inhibitors of human beta-secretase. Part 2.
abstract: We describe an optimized series of acyclic hydroxyethylamine transition state isosteres of beta-secretase that incorporates a variety of P(2) side chains that yield potent inhibitors with excellent cellular activity. A 2.2A crystal structure of compound 13 is shown.
authors.affiliation: Pfizer Inc., 700N. Chesterfield Pkwy., St. Louis, MO 63198, USA.
authors.forename: John N
authors.initials: JN
authors.lastname: Freskos
authors.forename: Yvette M
authors.initials: YM
authors.lastname: Fobian
authors.forename: Timothy E
authors.initials: TE
authors.lastname: Benson
authors.forename: Joseph B
authors.initials: JB
authors.lastname: Moon
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Bienkowski
authors.forename: David L
authors.initials: DL
authors.lastname: Brown
authors.forename: Thomas L
authors.initials: TL
authors.lastname: Emmons
authors.forename: Robert
authors.initials: R
authors.lastname: Heintz
authors.forename: Alice
authors.initials: A
authors.lastname: Laborde
authors.forename: Joseph J
authors.initials: JJ
authors.lastname: McDonald
authors.forename: Brent V
authors.initials: BV
authors.lastname: Mischke
authors.forename: John M
authors.initials: JM
authors.lastname: Molyneaux
authors.forename: Patrick B
authors.initials: PB
authors.lastname: Mullins
authors.forename: D
authors.initials: D
authors.lastname: Bryan Prince
authors.forename: Donna J
authors.initials: DJ
authors.lastname: Paddock
authors.forename: Alfredo G
authors.initials: AG
authors.lastname: Tomasselli
authors.forename: Greg
authors.initials: G
authors.lastname: Winterrowd
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy*; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002219:Carbamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D002478:Cells, Cultured; D015195:Drug Design; D006801:Humans; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D002219:Carbamates; D011480:Protease Inhibitors; D013449:Sulfonamides; D053829:Amyloid Precursor Protein Secretases