2(S)-(Cycloalk-1-enecarbonyl)-1-(4-phenyl-butanoyl)pyrrolidines and 2(S)-(aroyl)-1-(4-phenylbutanoyl)pyrrolidines as prolyl oligopeptidase inhibitors.
In order to replace the P2-P1 amide group, different 1-cycloalkenyls and 2-aryls were studied in the place of the P1 pyrrolidine group of a 4-phenylbutanoyl-L-Pro-pyrrolidine structure, which is a well-known prolyl oligopeptidase inhibitor SUAM-1221. The 1-cyclopentenyl and the 2-thienyl groups gave novel compounds, which were equipotent with the corresponding pyrrolidine-analog SUAM-1221. It was shown that the P2-P1 amide group of POP inhibitors can be replaced by an alpha,beta-unsaturated carbonyl group or the aryl conjugated carbonyl group.
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
Poutiainen
Sami
S
Leskinen
Harri
H
Vepsäläinen
Jouko
J
Christiaans
Johannes A M
JA
Forsberg
Markus M
MM
Männistö
Pekka T
PT
Wallén
Erik A A
EA
D000818:Animals; D009682:Magnetic Resonance Spectroscopy; D000085822:Prolyl Oligopeptidases; D011480:Protease Inhibitors / Q000494:pharmacology*; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology*; D012697:Serine Endopeptidases / Q000187:drug effects*; D021241:Spectrometry, Mass, Electrospray Ionization; D013552:Swine
D011480:Protease Inhibitors; D011759:Pyrrolidines; D012697:Serine Endopeptidases; D000085822:Prolyl Oligopeptidases