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Synthesis, radiolabeling and bioevaluation of a novel arylpiperazine derivative containing triazole as a 5-HT1Areceptor imaging agents

Elsevier Inc.
DOI: 10.1016/j.nucmedbio.2012.10.004
  • 5-Ht1Areceptor
  • Way100635
  • 99Mtc-Tricarbonyl
  • Click Chemistry
  • Biology
  • Chemistry
  • Medicine
  • Pharmacology


Abstract Introduction It has been recognized that serotonin plays a main role in various pathological conditions such as anxiety, depression, aggressiveness, schizophrenia, suicidal behavior, panic and autism. 1-(2-Methoxyphenyl) piperazine pharmacophore, a fragment of the true 5-HT1A antagonist WAY100635, is found in numerous selective 5-HT1A imaging agents. In this paper, we have reported the synthesis of a novel derivative of 1-(2-methoxyphenyl) piperazine that is labeled with 99mTc (CO)3 via click chemistry. Methods The bidentate alkyne, propargylglycine was reacted with phenyl piperazine triazole derivative in the presence of a catalytic amount of Cu (I) to form tridentate ligand. The ligand was radiolabeled with the precursor [99mTc] [(H2O)3 (CO)3]+ and characterized by HPLC. The bioevaluation of radio labeled ligand was carried out in rats. Results Triazole complex was labeled by 99mTc-tricarbonyl and its radiochemical yield was more than >95% which was determined by HPLC. In vivo stability studies in human serum albumin show a 93% ratio of complex after a 24h period. The calculated partition coefficient (logP) was 0.34±0.02. Receptor binding assays indicated about 70% specific binding of radioligand to 5-HT1A receptors. Biodistribution studies have shown brain hippocampus uptake of 0.40±0.08 %ID/g at 30min post injection. Conclusions Results indicate that this 99mTc-tricabonyl-arylpiperazine derivative has specific binding to 5-HT1A receptors and presented suitable characters for its use as a CNS imaging agent.

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