Dipeptide vinyl sultams: synthesis via the Wittig-Horner reaction and activity against papain, falcipain-2 and Plasmodium falciparum.
The synthesis of phosphonate derivatives of N-phenyl- and N-benzyl-gamma- and delta-sultams, and their application in the Wittig-Horner reaction with N-Boc-L-phenylalanine aldehyde to afford E- and Z-isomers, are described. These compounds were further processed to provide five dipeptide vinyl sultams, which were found to be inactive against papain at concentrations up to 50 microM. In contrast, vinyl sultams demonstrated weak activity against recombinant falcipain-2 and Plasmodium falciparum W2.
Valente
Cláudia
C
CECF, Faculty of Pharmacy, University of Lisbon, Avenida das Forças Armadas, Lisboa 1600-083, Portugal, and Department of Medicine, San Francisco General Hospital, University of California 94143-0811, USA.
Guedes
Rita C
RC
Moreira
Rui
R
Iley
Jim
J
Gut
Jiri
J
Rosenthal
Philip J
PJ
D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D003546:Cysteine Endopeptidases / Q000187:drug effects*; D004151:Dipeptides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008958:Models, Molecular; D010206:Papain / Q000187:drug effects*; D010963:Plasmodium falciparum / Q000187:drug effects*
D000962:Antimalarials; D004151:Dipeptides; D003546:Cysteine Endopeptidases; C416224:falcipain 2; D010206:Papain