Synthesis, in vitro and in vivo evaluation of [O-methyl-11C] 2-{4-[4-(3-methoxyphenyl)piperazin-1-yl]-butyl}-4-methyl-2H-[1,2,4]-triazine-3,5-dione:: A novel agonist 5-HT1A receptor PET ligand

被引：20

作者：

Prabhakaran, J

Parsey, RV

Majo, VJ

Hsiung, SC

Milak, MS

Tamir, H

Simpson, NR

Van Heertum, RL

Mann, JJ

Kumar, JSD ^{[1
]}

机构：

[1] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Psychiat, New York, NY 10032 USA

[2] Columbia Univ Coll Phys & Surg, New York State Psychiat Inst, Dept Radiol, New York, NY 10032 USA

[3] New York State Psychiat Inst & Hosp, Dept Neurosci, New York, NY 10032 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2006年 / 16卷 / 08期

关键词：

C-11]MMT; positron emission tomography; agonism; radiotracer;

D O I：

10.1016/j.bmcl.2006.01.052

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Synthesis and in vivo evaluation of 2-{4-[4-(3-methoxyphenyl)piperazin-1-yl]-butyl}-4-methyl-2H-[1,2,4]triazine-3,5-dione (5 or MMT), a high affinity and selective serotonin 5-HT1AR agonist PET tracer, are described. GTP gamma S assay shows that MMT is an agonist with an EC50 comparable to 5-HT. Radiolabeling of 5 was achieved in 30% yield (EOS) from desmethyl-MMT (4) with >99% chemical and radiochemical purities and a specific activity >1000 Ci/mmol. PET Studies in baboon show that [C-11]5 penetrates the blood-brain barrier but, because of low specific binding and fast clearance of radioactivity it is not a suitable PET tracer for the in vivo quantification of 5-HT1AR. (C) 2006 Elsevier Ltd. All rights reserved.

引用

收藏

页码：2101 / 2104

页数：4

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