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.

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收藏

页码：5568 / 5570

页数：3

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