An introduction of a pyridine group into the structure of prolyl oligopeptidase inhibitors.
A series of ionizable prolyl oligopeptidase inhibitors were developed through the introduction of a pyridyl group to the P3 position of the prolyl oligopeptidase inhibitor structure. The study was performed on previously developed prolyl oligopeptidase inhibitors with proline mimetics at the P2 position. The 3-pyridyl group resulted in equipotent compounds as compared to the parent compounds. It was shown that the pyridyl group improves water solubility and, in combination with a 5(R)-tert-butyl-l-prolyl group at the P2 position, good lipophilicity can be achieved.
Jarho
Elina M
EM
Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, FI-70211 Kuopio, Finland. Elina.Jarho@uku.fi
Venäläinen
Jarkko I
JI
Juntunen
Juha
J
Yli-Kokko
A Leena
AL
Vepsäläinen
Jouko
J
Christiaans
Johannes A M
JA
Forsberg
Markus M
MM
Järvinen
Tomi
T
Männistö
Pekka T
PT
Wallén
Erik A A
EA
D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D000085822:Prolyl Oligopeptidases; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000378:metabolism*
D004791:Enzyme Inhibitors; D011725:Pyridines; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases