title: Dipeptidyl alpha-fluorovinyl Michael acceptors: synthesis and activity against cysteine proteases.
abstract: The synthesis of novel dipeptidyl alpha-fluorovinyl sulfones using a Horner-Wadsworth-Emmons approach on N-Boc-l-phenylalaninal is described. Inhibitory assays against a Leishmania mexicana cysteine protease (CPB2.8DeltaCTE) revealed low biological activity. Relative rates of Michael additions of 2'-(phenethyl)thiol with vinyl sulfone and alpha-fluorovinyl sulfone were determined, and ab initio calculations on several Michael acceptor model structures were performed; both were in agreement with the biological testing results.
authors.affiliation: Laboratory of Medicinal Chemistry, University of Antwerp, Universiteitsplein 1, BE-2610 Antwerp, Belgium.
authors.forename: Koen
authors.initials: K
authors.lastname: Steert
authors.forename: Ibrahim
authors.initials: I
authors.lastname: El-Sayed
authors.forename: Pieter
authors.initials: P
authors.lastname: Van der Veken
authors.forename: Alisa
authors.initials: A
authors.lastname: Krishtal
authors.forename: Christian
authors.initials: C
authors.lastname: Van Alsenoy
authors.forename: Gareth D
authors.initials: GD
authors.lastname: Westrop
authors.forename: Jeremy C
authors.initials: JC
authors.lastname: Mottram
authors.forename: Graham H
authors.initials: GH
authors.lastname: Coombs
authors.forename: Koen
authors.initials: K
authors.lastname: Augustyns
authors.forename: Achiel
authors.initials: A
authors.lastname: Haemers
mesh_terms: D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D003546:Cysteine Endopeptidases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D004151:Dipeptides / Q000138:chemical synthesis* / Q000494:pharmacology; D007894:Leishmania mexicana / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D016773:Leishmaniasis, Cutaneous / Q000188:drug therapy / Q000201:enzymology / Q000469:parasitology; D008958:Models, Molecular
chemical_list: D015853:Cysteine Proteinase Inhibitors; D004151:Dipeptides; D003546:Cysteine Endopeptidases