Selective mGAT2 (BGT-1) GABA Uptake Inhibitors: Design, Synthesis, and Pharmacological Characterization

被引：32
|
作者：
Vogensen, Stine B. [1 ]
Jorgensen, Lars [1 ]
Madsen, Karsten K. [1 ]
Borkar, Nrupa [1 ]
Wellendorph, Petrine [1 ]
Skovgaard-Petersen, Jonas [1 ]
Schousboe, Arne [1 ]
White, H. Steve [2 ]
Krogsgaard-Larsen, Povl [1 ]
Clausen, Rasmus P. [1 ]
机构：
[1] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, DK-2100 Copenhagen, Denmark
[2] Univ Utah, Dept Pharmacol & Toxicol, Anticonvulsant Drug Dev Program, Salt Lake City, UT 84112 USA
来源：
JOURNAL OF MEDICINAL CHEMISTRY | 2013年 / 56卷 / 05期
关键词：
MOLECULAR PHARMACOLOGY; ANTICONVULSANT ACTION; FUNCTIONAL-ROLE; TRANSPORTERS; TIAGABINE; MECHANISMS; DRUGS;
D O I：
10.1021/jm301872x
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
beta-Amino acids sharing a lipophilic diaromatic side chain were synthesized and characterized pharmacologically on mouse GABA transporter subtypes mGAT1-4. The parent amino acids were also characterized. Compounds 13a, 13b, and 17b displayed more than 6-fold selectivity for mGAT2 over mGAT1. Compound 17b displayed anticonvulsive properties inferring a role of mGAT2 in epileptic disorders. These results provide new neuropharmacological tools and a strategy for designing subtype selective GABA transport inhibitors.
引用
收藏
页码：2160 / 2164
页数：5
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