Dicarboxylic acid bis(L-prolyl-pyrrolidine) amides as prolyl oligopeptidase inhibitors.
New dicarboxylic acid bis(L-prolyl-pyrrolidine) amides were synthesized, and their inhibitory activity against prolyl oligopeptidase from pig brain was tested in vitro. As compared with earlier described prolyl oligopeptidase inhibitors, these new compounds have in common an L-prolyl-pyrrolidine moiety, but the typical lipophilic acyl end group is replaced by another L-prolyl-pyrrolidine moiety connected symmetrically with a short dicarboxylic acid linker. These compounds are a new type of peptidomimetic prolyl oligopeptidase inhibitor.
Wallén
Erik A A
EA
Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FIN-70211 Kuopio, Finland. wallen@uku.fi
Christiaans
Johannes A M
JA
Forsberg
Markus M
MM
Venäläinen
Jarkko I
JI
Männistö
Pekka T
PT
Gynther
Jukka
J
D000577:Amides / Q000138:chemical synthesis* / Q000737:chemistry; D000818:Animals; D001921:Brain / Q000201:enzymology; D011392:Proline / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D000085822:Prolyl Oligopeptidases; D011759:Pyrrolidines / Q000138:chemical synthesis* / Q000737:chemistry; D012697:Serine Endopeptidases / Q000737:chemistry*; D015842:Serine Proteinase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013552:Swine
D000577:Amides; D011759:Pyrrolidines; D015842:Serine Proteinase Inhibitors; D011392:Proline; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases