Evaluation of 3-Ethyl-3-(phenylpiperazinylbutyl)oxindoles as PET Ligands for the Serotonin 5-HT7 Receptor: Synthesis, Pharmacology, Radio labeling, and in Vivo Brain Imaging in Pigs

被引：33

作者：

Herth, Matthias M. ^{[1
,2
,3
]}

Andersen, Valdemar L. ^{[1
,2
,3
]}

Hansen, Hanne D. ^{[1
,2
]}

Stroth, Nikolas ^{[4
,5
]}

Volk, Balazs ^{[6
]}

Lehel, Szabolcs ^{[7
]}

Dyssegaard, Agnete ^{[1
,2
]}

Ettrup, Anders ^{[1
,2
]}

Svenningsson, Per ^{[4
,5
]}

Knudsen, Gitte M. ^{[1
,2
]}

Kristensen, Jesper L. ^{[1
,2
,3
]}

机构：

[1] Rigshosp, Ctr Integrated Mol Brain Imaging, DK-2100 Copenhagen, Denmark

[2] Univ Copenhagen, DK-2100 Copenhagen, Denmark

[3] Univ Copenhagen, Fac Hlth & Med Sci, Dept Drug Design & Pharmacol, DK-2100 Copenhagen, Denmark

[4] Karolinska Inst, Dept Neurol & Clin Neurosci, Ctr Mol Med, S-17176 Stockholm, Sweden

[5] Karolinska Univ Hosp, S-17176 Stockholm, Sweden

[6] Egis Pharmaceut Plc, H-1475 Budapest, Hungary

[7] Rigshosp, PET & Cyclotron Unit, DK-2100 Copenhagen, Denmark

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2015年 / 58卷 / 08期

关键词：

INVERSE AGONIST; CB1; RECEPTOR; RADIOLIGANDS; AMISULPRIDE; ANTAGONIST; POTENT;

D O I：

10.1021/acs.jmedchem.5b00095

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

We have investigated several oxindole derivatives in the pursuit of a 5-HT7 receptor PET ligand. Herein the synthesis, chiral separation, and pharmacological profiling of two possible PET candidates toward a wide selection of CNS-targets are detailed. Subsequent C-11-labeling and in vivo evaluation in Danish landrace pigs showed that both ligands displayed high brain uptake. However, neither of the radioligands could be displaced by the 5-HT7 receptor selective inverse agonist SB-269970.

引用

收藏

页码：3631 / 3636

页数：6

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