A cyclopent-2-enecarbonyl group mimics proline at the P2 position of prolyl oligopeptidase inhibitors

Elina M Jarho; Jarkko I Venäläinen; Juhani Huuskonen; Johannes A M Christiaans; J Arturo Garcia-Horsman; Markus M Forsberg; Tomi Järvinen; Jukka Gynther; Pekka T Männistö; Erik A A Wallén

doi:10.1021/jm049503w

A cyclopent-2-enecarbonyl group mimics proline at the P2 position of prolyl oligopeptidase inhibitors

J Med Chem. 2004 Nov 4;47(23):5605-7. doi: 10.1021/jm049503w.

Authors

Elina M Jarho¹, Jarkko I Venäläinen, Juhani Huuskonen, Johannes A M Christiaans, J Arturo Garcia-Horsman, Markus M Forsberg, Tomi Järvinen, Jukka Gynther, Pekka T Männistö, Erik A A Wallén

Affiliation

¹ Department of Pharmaceutical Chemistry, University of Kuopio, P.O. Box 1627, FI-70211 Kuopio, Finland. [email protected]

PMID: 15509157
DOI: 10.1021/jm049503w

Abstract

With the aim to replace the natural amino acid proline by a proline mimetic structure, a cyclopent-2-enecarbonyl moiety was studied at the P2 position of prolyl oligopeptidase (POP) inhibitors. The cyclopent-2-enecarbonyl moiety proved to be an excellent proline mimetic at the P2 position of POP inhibitors. The replacement is particularly useful when increased lipophilicity is needed.

Publication types

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

MeSH terms

1-Octanol
Animals
Brain / drug effects
Brain / enzymology
Buffers
Cyclopentanes / chemical synthesis
Cyclopentanes / chemistry*
Cyclopentanes / pharmacology
In Vitro Techniques
Molecular Mimicry
Proline / chemistry*
Prolyl Oligopeptidases
Serine Endopeptidases / metabolism*
Serine Proteinase Inhibitors / chemical synthesis
Serine Proteinase Inhibitors / chemistry*
Serine Proteinase Inhibitors / pharmacology
Solubility
Structure-Activity Relationship
Swine

Substances

Buffers
Cyclopentanes
Serine Proteinase Inhibitors
Proline
Serine Endopeptidases
Prolyl Oligopeptidases
1-Octanol