title: Synthesis and in vivo evaluation of cyclic diaminopropane BACE-1 inhibitors.
abstract: The synthesis, evaluation, and structure-activity relationships of a set of related constrained diaminopropane inhibitors of BACE-1 are described. The full in vivo profile of an optimized inhibitor in both normal and P-gp deficient mice is compared with data generated in normal rats.
authors.affiliation: Bristol-Myers Squibb Research and Development, 5 Research Parkway, Wallingford, CT 06492, USA. lorin.thompson@bms.com
authors.forename: Lorin A
authors.initials: LA
authors.lastname: Thompson
authors.forename: Jianliang
authors.initials: J
authors.lastname: Shi
authors.forename: Carl P
authors.initials: CP
authors.lastname: Decicco
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Tebben
authors.forename: Richard E
authors.initials: RE
authors.lastname: Olson
authors.forename: Kenneth M
authors.initials: KM
authors.lastname: Boy
authors.forename: Jason M
authors.initials: JM
authors.lastname: Guernon
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Good
authors.forename: Ann
authors.initials: A
authors.lastname: Liauw
authors.forename: Changsheng
authors.initials: C
authors.lastname: Zheng
authors.forename: Robert A
authors.initials: RA
authors.lastname: Copeland
authors.forename: Andrew P
authors.initials: AP
authors.lastname: Combs
authors.forename: George L
authors.initials: GL
authors.lastname: Trainor
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Camac
authors.forename: Jodi K
authors.initials: JK
authors.lastname: Muckelbauer
authors.forename: Kimberley A
authors.initials: KA
authors.lastname: Lentz
authors.forename: James E
authors.initials: JE
authors.lastname: Grace
authors.forename: Catherine R
authors.initials: CR
authors.lastname: Burton
authors.forename: Jeremy H
authors.initials: JH
authors.lastname: Toyn
authors.forename: Donna M
authors.initials: DM
authors.lastname: Barten
authors.forename: Jovita
authors.initials: J
authors.lastname: Marcinkeviciene
authors.forename: Jere E
authors.initials: JE
authors.lastname: Meredith
authors.forename: Charles F
authors.initials: CF
authors.lastname: Albright
authors.forename: John E
authors.initials: JE
authors.lastname: Macor
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000544:Alzheimer Disease / Q000188:drug therapy; D053829:Amyloid Precursor Protein Secretases / Q000037:antagonists & inhibitors* / Q000378:metabolism*; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018360:Crystallography, X-Ray; D003959:Diamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology*; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D051381:Rats; D013329:Structure-Activity Relationship
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003959:Diamines; D004791:Enzyme Inhibitors; C070006:1,2-diaminopropane; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human