title: Structure-based design of cycloamide-urethane-derived novel inhibitors of human brain memapsin 2 (beta-secretase).
abstract: A series of novel macrocyclic amide-urethanes was designed and synthesized based upon the X-ray crystal structure of our lead inhibitor (1, OM99-2 with eight residues) bound to memapsin 2. Ring size and substituent effects have been investigated. Cycloamide-urethanes containing 14- to 16-membered rings exhibited low nanomolar inhibitory potencies against human brain memapsin 2 (beta-secretase).
authors.affiliation: Department of Chemistry, University of Illinois at Chicago, 845 West Taylor Street, Chicago, IL 60607, USA. arunghos@uic.edu
authors.forename: Arun K
authors.initials: AK
authors.lastname: Ghosh
authors.forename: Thippeswamy
authors.initials: T
authors.lastname: Devasamudram
authors.forename: Lin
authors.initials: L
authors.lastname: Hong
authors.forename: Christopher
authors.initials: C
authors.lastname: DeZutter
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Xu
authors.forename: Vajira
authors.initials: V
authors.lastname: Weerasena
authors.forename: Gerald
authors.initials: G
authors.lastname: Koelsch
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Bilcer
authors.forename: Jordan
authors.initials: J
authors.lastname: Tang
mesh_terms: D000577:Amides / Q000737:chemistry*; D053829:Amyloid Precursor Protein Secretases; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D001921:Brain / Q000201:enzymology*; D018360:Crystallography, X-Ray; D010450:Endopeptidases; D006801:Humans; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D014520:Urethane / Q000737:chemistry*
chemical_list: D000577:Amides; D011480:Protease Inhibitors; D014520:Urethane; D053829:Amyloid Precursor Protein Secretases; D010450:Endopeptidases; D016282:Aspartic Acid Endopeptidases; C509280:BACE1 protein, human