Irreversible inhibition of dipeptidyl peptidase 8 by dipeptide-derived diaryl phosphonates

被引：48
|
作者：
Van der Veken, Pieter
Soroka, Anna
Brandt, Inger
Chen, Yuan-Shou
Maes, Marie-Berthe
Lambeir, Anne-Marie
Chen, Xin
Haemers, Achiel
Scharpe, Simon
Augustyns, Koen
De Meester, Ingrid
机构：
[1] Univ Antwerp, Med Chem Lab, B-2610 Antwerp, Belgium
[2] Univ Antwerp, Med Biochem Lab, B-2610 Antwerp, Belgium
[3] Natl Hlth Res Inst, Div Biotechnol & Pharmaceut Res, Zhu Nan 350, Miaoli, Taiwan
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2007年 / 50卷 / 23期
关键词：
D O I：
10.1021/jm701005a
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Dipeptide-derived compounds, bearing various P2 residues and a diaryl pyrrolidin-2-yl phosphonate at the PI position, were evaluated as dipeptidyl peptidase 8 (DPP8) inhibitors. With these products, irreversible inhibition of DPP8 was observed. To obtain inhibitors with an improved activity and selectivity profile, a set of selected analogues containing a diaryl isoindolin-1-ylphosphonate at P1 was synthesized and evaluated. Within this latter series, compound 2e was shown to be a potent, irreversible inhibitor of DPP8, demonstrating very low affinity for DPP IV and DPP II.
引用
收藏
页码：5568 / 5570
页数：3
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