Sulfamide as Zinc Binding Motif in Small Molecule Inhibitors of Activated Thrombin Activatable Fibrinolysis Inhibitor (TAFIa)

被引：9

作者：

Halland, Nis ^{[1
]}

Czech, Joerg ^{[1
]}

Czechtizky, Werngard ^{[1
]}

Evers, Andreas ^{[1
]}

Follmann, Markus ^{[1
,2
]}

Kohlmann, Markus ^{[1
]}

Schreuder, Herman A. ^{[1
]}

Kallus, Christopher ^{[1
,3
]}

机构：

[1] Sanofi R&D, Ind Pk Hochst Bldg G838, D-65926 Frankfurt, Germany

[2] Bayer Pharma AG, Aprather Weg 18A, D-42113 Wuppertal, Germany

[3] Bayer Cropsci, Ind Pk Hochst Bldg G836, D-65926 Frankfurt, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2016年 / 59卷 / 20期

关键词：

PROCARBOXYPEPTIDASE-B; CARBOXYPEPTIDASE-N; ARGININE; PLASMA; TARGET; STATE;

D O I：

10.1021/acs.jmedchem.6b01276

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Previously disclosed TAFIa inhibitors having a urea zinc-binding motif were used as the starting point for the development of a novel class of highly potent inhibitors having a sulfamide zinc-binding motif. High-resolution X-ray cocrystal structures were used to optimize the structures and reveal a highly unusual sulfamide configuration. A selected sulfamide was profiled in vitro and in vivo and displayed a promising ADMET profile.

引用

页码：9567 / 9573

页数：7

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