title: An introduction of a pyridine group into the structure of prolyl oligopeptidase inhibitors.
abstract: 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.
authors.affiliation: Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, FI-70211 Kuopio, Finland. Elina.Jarho@uku.fi
authors.forename: Elina M
authors.initials: EM
authors.lastname: Jarho
authors.forename: Jarkko I
authors.initials: JI
authors.lastname: Venäläinen
authors.forename: Juha
authors.initials: J
authors.lastname: Juntunen
authors.forename: A Leena
authors.initials: AL
authors.lastname: Yli-Kokko
authors.forename: Jouko
authors.initials: J
authors.lastname: Vepsäläinen
authors.forename: Johannes A M
authors.initials: JA
authors.lastname: Christiaans
authors.forename: Markus M
authors.initials: MM
authors.lastname: Forsberg
authors.forename: Tomi
authors.initials: T
authors.lastname: Järvinen
authors.forename: Pekka T
authors.initials: PT
authors.lastname: Männistö
authors.forename: Erik A A
authors.initials: EA
authors.lastname: Wallén
mesh_terms: D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D000085822:Prolyl Oligopeptidases; D011725:Pyridines / Q000737:chemistry* / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000378:metabolism*
chemical_list: D004791:Enzyme Inhibitors; D011725:Pyridines; D012697:Serine Endopeptidases; C000705287:PREPL protein, human; D000085822:Prolyl Oligopeptidases