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

页码：2160 / 2164

页数：5

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