Title : Gamma-amino-substituted analogues of 1-[(S)-2,4-diaminobutanoyl]piperidine as highly potent and selective dipeptidyl peptidase II inhibitors - Senten_2004_J.Med.Chem_47_2906 |
Author(s) : Senten K , Van der Veken P , De Meester I , Lambeir AM , Scharpe S , Haemers A , Augustyns K |
Ref : Journal of Medicinal Chemistry , 47 :2906 , 2004 |
Abstract :
Using 1-[(S)-2,4-diaminobutanoyl]piperidine as lead compound, we developed a large series of highly potent and selective dipeptidyl peptidase II (DPP II) inhibitors. gamma-Amino substitution with arylalkyl groups, for example, a 2-chlorobenzyl moiety, resulted in a DPP II inhibitor with an IC(50) = 0.23 nM and a high selectivity toward DPP IV (IC(50) = 345 microM). Furthermore, it was shown that the basicity of the gamma-amino is important and that alpha-amino substitution is not favorable. Piperidine-2-nitriles did not show an increase in potency but rather reduced the selectivity. Introduction of a 4-methyl or a 3-fluorine on piperidine improved selectivity and preserved the high potency. |
PubMedSearch : Senten_2004_J.Med.Chem_47_2906 |
PubMedID: 15139769 |
Senten K, Van der Veken P, De Meester I, Lambeir AM, Scharpe S, Haemers A, Augustyns K (2004)
Gamma-amino-substituted analogues of 1-[(S)-2,4-diaminobutanoyl]piperidine as highly potent and selective dipeptidyl peptidase II inhibitors
Journal of Medicinal Chemistry
47 :2906
Senten K, Van der Veken P, De Meester I, Lambeir AM, Scharpe S, Haemers A, Augustyns K (2004)
Journal of Medicinal Chemistry
47 :2906