| Autor: |
Senten, K., Veken, P. Van der, Meester, I. De, Lambeir, A.-M., Scharpe, S., Haemers, A., Augustyns, K. |
| Zdroj: |
Journal of Medicinal Chemistry; May 2004, Vol. 47 Issue: 11 p2906-2916, 11p |
| Abstrakt: |
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. |
| Databáze: |
Supplemental Index |
| Externí odkaz: |
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