124730-07-0Relevant academic research and scientific papers
γ-amino-substituted analogues of 1-[(S)-2,4-diaminobutanoyl]piperidine as highly potent and selective dipeptidyl peptidase II inhibitors
Senten, Kristel,Van Der Veken, Pieter,De Meester, Ingrid,Lambeir, Anne-Marie,Scharpé, Simon,Haemers, Achiel,Augustyns, Koen
, p. 2906 - 2916 (2007/10/03)
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. γ-Amino substitution with arylalkyl groups, for example, a 2-chlorobenzyl moiety, resulted in a DPP II inhibitor with an IC50 = 0.23 nM and a high selectivity toward DPP IV (IC50 = 345 μM). Furthermore, it was shown that the basicity of the γ-amino is important and that α-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.
