2(S)-(Cycloalk-1-enecarbonyl)-1-(4-phenyl-butanoyl)pyrrolidines and 2(S)-(aroyl)-1-(4-phenylbutanoyl)pyrrolidines as prolyl oligopeptidase inhibitors

Elina M Jarho; Jarkko I Venäläinen; Sami Poutiainen; Harri Leskinen; Jouko Vepsäläinen; Johannes A M Christiaans; Markus M Forsberg; Pekka T Männistö; Erik A A Wallén

doi:10.1016/j.bmc.2006.12.036

2(S)-(Cycloalk-1-enecarbonyl)-1-(4-phenyl-butanoyl)pyrrolidines and 2(S)-(aroyl)-1-(4-phenylbutanoyl)pyrrolidines as prolyl oligopeptidase inhibitors

Bioorg Med Chem. 2007 Mar 1;15(5):2024-31. doi: 10.1016/j.bmc.2006.12.036. Epub 2006 Dec 24.

Authors

Elina M Jarho¹, Jarkko I Venäläinen, Sami Poutiainen, Harri Leskinen, Jouko Vepsäläinen, Johannes A M Christiaans, Markus M Forsberg, Pekka T Männistö, Erik A A Wallén

Affiliation

¹ Department of Pharmaceutical Chemistry, University of Kuopio, PO Box 1627, FI-70211 Kuopio, Finland. Elina.Jarho@uku.fi

PMID: 17215128
DOI: 10.1016/j.bmc.2006.12.036

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Magnetic Resonance Spectroscopy
Prolyl Oligopeptidases
Protease Inhibitors / pharmacology*
Pyrrolidines / chemistry
Pyrrolidines / pharmacology*
Serine Endopeptidases / drug effects*
Spectrometry, Mass, Electrospray Ionization
Swine

Substances

Protease Inhibitors
Pyrrolidines
Serine Endopeptidases
Prolyl Oligopeptidases