Prolylisoxazoles: potent inhibitors of prolyloligopeptidase with antitrypanosomal activity.
Prolylprolylisoxazoles and prolylprolylisoxazolines were synthesized through a 1,3-dipolar cycloaddition reaction. These compounds are potent inhibitors of human and trypanosomal prolyloligopeptidase. They were shown to inhibit Trypanosoma cruzi and Trypanosoma b. brucei in in vitro systems with ED(50)'s in the lower microM range.
Bal
Gunther
G
Department of Medicinal Chemistry, University of Antwerp, Belgium.
Van der Veken
Pieter
P
Antonov
Dimitri
D
Lambeir
Anne-Marie
AM
Grellier
Philippe
P
Croft
Simon L
SL
Augustyns
Koen
K
Haemers
Achiel
A
D000818:Animals; D006801:Humans; D007555:Isoxazoles / Q000138:chemical synthesis / Q000494:pharmacology*; D000085822:Prolyl Oligopeptidases; D011480:Protease Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000378:metabolism*; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000201:enzymology; D014351:Trypanosomatina / Q000187:drug effects
D007555:Isoxazoles; D011480:Protease Inhibitors; D014344:Trypanocidal Agents; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases