Synthesis and dipeptidyl peptidase inhibition of N-(4-substituted-2,4-diaminobutanoyl)piperidines

Anna Soroka; Pieter Van der Veken; Ingrid De Meester; Anne-Marie Lambeir; Marie-Berthe Maes; Simon Scharpé; Achiel Haemers; Koen Augustyns

doi:10.1016/j.bmcl.2006.06.082

Synthesis and dipeptidyl peptidase inhibition of N-(4-substituted-2,4-diaminobutanoyl)piperidines

Bioorg Med Chem Lett. 2006 Sep 15;16(18):4777-9. doi: 10.1016/j.bmcl.2006.06.082. Epub 2006 Jul 17.

Authors

Anna Soroka¹, Pieter Van der Veken, Ingrid De Meester, Anne-Marie Lambeir, Marie-Berthe Maes, Simon Scharpé, Achiel Haemers, Koen Augustyns

Affiliation

¹ Laboratory of Medicinal Chemistry University of Antwerp, Universiteitsplein 1, B-2610 Antwerp, Belgium.

PMID: 16844373
DOI: 10.1016/j.bmcl.2006.06.082

Abstract

In this paper, we report the synthesis of diastereomerically pure N-(4-substituted-2,4-diaminobutanoyl)piperidines. These compounds were prepared to investigate the influence of the 4-substitution on the dipeptidyl peptidase II (DPP II) activity and selectivity of the parent N-(2,4-diaminobutanoyl)piperidine. The (4S)-methyl compound showed subnanomolar inhibition, comparable with the parent compound. The (4R)-methyl group or bigger substituents decreased the activity.

Publication types

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

MeSH terms

Amination
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / antagonists & inhibitors*
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / metabolism
Inhibitory Concentration 50
Molecular Structure
Piperidines / chemical synthesis
Piperidines / chemistry*
Piperidines / pharmacology*
Protease Inhibitors / chemical synthesis*
Protease Inhibitors / chemistry
Protease Inhibitors / pharmacology*
Stereoisomerism

Substances

Piperidines
Protease Inhibitors
piperidine
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
dipeptidyl peptidase II