Modified 3-alkyl-1,8-dibenzylxanthines as GTP-competitive inhibitors of phosphoenolpyruvate carboxykinase

被引：23
作者：
Foley, LH
Wang, P
Dunten, P
Ramsey, G
Gubler, ML
Wertheimer, SJ
机构：
[1] Hoffmann La Roche Inc, Roche Res Ctr, Dept Discovery Chem, Nutley, NJ 07110 USA
[2] Hoffmann La Roche Inc, Roche Res Ctr, Dept Metab Dis, Nutley, NJ 07110 USA
来源：
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2003年 / 13卷 / 20期
关键词：
D O I：
10.1016/S0960-894X(03)00722-4
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
The first non-substrate like inhibitors of human cytosolic phosphoenolpyruvate carboxykinase (PEPCK) competitive with GTP are reported. An effort to discover orally active compounds that improve glucose homeostasis in Type 2 diabetics by reversibly inhibiting PEPCK led to the discovery of 1-allyl-3-butyl-8-methylxanthine (5). We now report modifications at N-1 and C-8 that improved the in vitro activity of the initial xanthine HTS hit by 100-fold and a developing SAR for this class of inhibitor. (C) 2003 Elsevier Ltd. All rights reserved.
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页码：3607 / 3610
页数：4
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