Design, synthesis, and evaluation of a pyrrolinone-based matrix metalloprotease inhibitor.
[reaction: see text] A pyrrolinone-based hydroxamate matrix metalloprotease inhibitor, (-)-1, has been designed and synthesized. Enzymatic assay revealed that (-)-1 inhibited three of the ten matrix metalloprotease enzymes examined and as such represents a new, potentially important lead structure.
Smith
A B
AB
Department of Chemistry, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA. smithab@sas.upenn.edu
Nittoli
T
T
Sprengeler
P A
PA
Duan
J J
JJ
Liu
R Q
RQ
Hirschmann
R F
RF
D000447:Aldehydes; D015195:Drug Design; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D008958:Models, Molecular; D011480:Protease Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry
D000447:Aldehydes; D007527:Isoenzymes; D011480:Protease Inhibitors; D011758:Pyrroles; D008666:Metalloendopeptidases