Synthesis and preliminary PET study of the 5-HT7 receptor antagonist [11C]DR4446

Autor:	Jun Maeda, Kazutoshi Suzuki, Tetsuya Suhara, Terushi Haradahira, Takayo Kida, Ming-Rong Zhang, Takashi Okauchi, Shigeru Obayashi
Rok vydání:	2002
Předmět:	Bicyclic molecule Stereochemistry Chemistry medicine.drug_class Organic Chemistry Antagonist Desmethyl Receptor antagonist Biochemistry Chemical synthesis Analytical Chemistry 5-HT7 receptor Drug Discovery medicine Radiology Nuclear Medicine and imaging Specific activity Receptor Spectroscopy
Zdroj:	Journal of Labelled Compounds and Radiopharmaceuticals. 45:857-866
ISSN:	1099-1344 0362-4803
DOI:	10.1002/jlcr.606
Popis:	DR4446 (1-methyl-2a-[4-(4,5,6,7-tetrahydrothieno[3,2-c]pyridin-5-yl)butyl]-2a,3,4,5-tetrahydro-1H-benz[cd]indole-2-one) is a potent 5-HT7 receptor antagonist (Ki=9.7 nM) with a high selectivity over other 5-HT family receptors (Ki for 5-HT1A: 770 nM; for other 5-HT receptors: >1000 nM). As a positron emission tomography (PET) tracer for the 5-HT7 receptor, [11C]DR4446 was synthesized at high radiochemical purity ( >98%) with specific activity of 73–120 GBq/μmol at the end of synthesis by the alkylation of the desmethyl precursor (1) with [11C]CH3I in the presence of NaH. A PET study in monkey demonstrated that [11C]DR4446 had good permeability into the brain, and had a specific binding component in the brain regions including the thalamus, possibly an area in the 5-HT7 receptors. Metabolite analysis showed that [11C]DR4446 was relatively stable and low percentages of two radio-labeled metabolites were detected in the plasma of monkey using HPLC. Copyright © 2002 John Wiley & Sons, Ltd.
Databáze:	OpenAIRE
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