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.
Publication types
-
Comparative Study
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Animals
-
Binding Sites / drug effects
-
Cysteine Endopeptidases* / metabolism
-
Cysteine Proteinase Inhibitors / chemical synthesis*
-
Cysteine Proteinase Inhibitors / pharmacology
-
Dipeptides / chemical synthesis*
-
Dipeptides / pharmacology
-
Leishmania mexicana / drug effects
-
Leishmania mexicana / enzymology
-
Leishmania mexicana / growth & development
-
Leishmaniasis, Cutaneous / drug therapy
-
Leishmaniasis, Cutaneous / enzymology
-
Leishmaniasis, Cutaneous / parasitology
-
Models, Molecular
Substances
-
Cysteine Proteinase Inhibitors
-
Dipeptides
-
Cysteine Endopeptidases