The reversed binding of β-phenethylamine inhibitors of DPP-IV:: X-ray structures and properties of novel fragment and elaborated inhibitors

被引：31

作者：

Nordhoff, S

Cerezo-Gálvez, S

Feurer, A

Hill, O

Matassa, VG

Metz, G

Rummey, C

Thiemann, M

Edwards, PJ

机构：

[1] Santhera Pharmaceut, Med Chem, D-69120 Heidelberg, Germany

[2] Santhera Pharmaceut, Biochemistry, D-69120 Heidelberg, Germany

[3] Santhera Pharmaceut, Computat Discovery, D-69120 Heidelberg, Germany

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 06期

关键词：

dipeptidyl peptidase-IV; DPP-IV; type; 2; diabetes; glucagon-like peptide-1; GLP-1;

D O I：

10.1016/j.bmcl.2005.11.103

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The co-crystal structure of beta-phenethylamine fragment inhibitor 5 bound to DPP-IV revealed that the phenyl ring occupied the proline pocket of the enzyme. This finding provided the basis for a general hypothesis of a reverse binding mode for beta-phenethylamine-based DPP-IV inhibitors. Novel inhibitor design concepts that obviate substrate-like structure-activity relationships (SAR) were thereby enabled, and novel, potent inhibitors were discovered. (C) 2005 Elsevier Ltd. All rights reserved.

引用

收藏

页码：1744 / 1748

页数：5

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