title: Synthesis, radiolabeling and bioevaluation of a novel arylpiperazine derivative containing triazole as a 5-HT1A receptor imaging agents.
abstract: BACKGROUND
  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-HT(1A) antagonist WAY100635, is found in numerous selective 5-HT(1A) imaging agents. In this paper, we have reported the synthesis of a novel derivative of 1-(2-methoxyphenyl) piperazine that is labeled with (99m)Tc (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 [(99m)Tc] [(H(2)O)(3) (CO)(3)](+) and characterized by HPLC. The bioevaluation of radio labeled ligand was carried out in rats.
  
  
  RESULTS
  Triazole complex was labeled by (99m)Tc-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-HT(1A) receptors. Biodistribution studies have shown brain hippocampus uptake of 0.40±0.08 %ID/g at 30 min post injection.
  
  
  CONCLUSIONS
  Results indicate that this (99m)Tc-tricabonyl-arylpiperazine derivative has specific binding to 5-HT(1A) receptors and presented suitable characters for its use as a CNS imaging agent.
authors.affiliation: Department of Medicinal Chemistry, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
authors.forename: Leila
authors.initials: L
authors.lastname: Hassanzadeh
authors.forename: Mostafa
authors.initials: M
authors.lastname: Erfani
authors.forename: Reza
authors.initials: R
authors.lastname: Najafi
authors.forename: Mohammad
authors.initials: M
authors.lastname: Shafiei
authors.forename: Mohsen
authors.initials: M
authors.lastname: Amini
authors.forename: Abbass
authors.initials: A
authors.lastname: Shafiee
authors.forename: Seyed Esmaeil Sadat
authors.initials: SE
authors.lastname: Ebrahimi
mesh_terms: D000818:Animals; D001386:Azides / Q000737:chemistry; D060326:Chemistry Techniques, Synthetic; D057930:Click Chemistry; D007553:Isotope Labeling; D057054:Molecular Imaging / Q000379:methods*; D015609:Organotechnetium Compounds / Q000737:chemistry; D000077489:Piperazine; D010879:Piperazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D044282:Receptor, Serotonin, 5-HT1A / Q000378:metabolism*; D014230:Triazoles / Q000737:chemistry*
chemical_list: D001386:Azides; D015609:Organotechnetium Compounds; D010879:Piperazines; D014230:Triazoles; D044282:Receptor, Serotonin, 5-HT1A; D000077489:Piperazine