508174-24-1Relevant academic research and scientific papers
Synthesis, structure activity relationship, radiolabeling and preclinical evaluation of high affinity ligands for the ion channel of the N-methyl-d-aspartate receptor as potential imaging probes for positron emission tomography
Klein, Pieter J.,Christiaans, Johannes A.M.,Metaxas, Athanasios,Schuit, Robert C.,Lammertsma, Adriaan A.,Van Berckel, Bart N.M.,Windhorst, Albert D.
, p. 1189 - 1206 (2015/03/04)
The N-methyl-d-aspartate receptor (NMDAr) is involved in many neurological and psychiatric disorders including Alzheimer's disease and schizophrenia. Currently, it is not possible to assess NMDAr availability in vivo. The purpose of this study was to develop a positron emission tomography (PET) ligand for the NMDAr ion channel. A series of di- and tri-N-substituted diarylguanidines was synthesized. In addition, in vitro binding affinity for the NMDAr ion channel in rat forebrain membrane fractions was assessed. Compounds 10, 11 and 32 were radiolabeled with either carbon-11 or fluorine-18. Ligands [11C]10 and [18F]32 were evaluated ex vivo in B6C3 mice. Biodistribution studies showed higher uptake of [11C]10 and [18F]32 in forebrain regions compared with cerebellum. In addition, for [11C]10 54% and for [18F]32 70% of activity in the brain at 60 min was due to intact tracer. Pre-treatment with MK-801 (0.6 mg·kg-1, ip) slightly decreased uptake in NMDAr-specific regions for [18F]32, but not for [11C]10. As such [18F]32 has the best characteristics as a PET tracer for the ion channel of the NMDAr.
Synthesis of [11C] N-(2-chloro-5-thiomethylphenyl)-N′-(3-methoxyphenyl)- N′-methylguanidine ([11C]GMOM): A candidate PET tracer for imaging the PCP site of the NMDA ion channel
Waterhouse, Rikki N.,Dumont, Filip,Sultana, Abida,Simpson, Norman,Laruelle, Marc
, p. 955 - 964 (2007/10/03)
The N-methyl-D-aspartate (NMDA) ion channel plays an important role in a number of neurodegenerative disorders including stroke, Parkinson's disease, Huntington's Chorea, Alzheimer's disease, schizophrenia and epilepsy. To provide effective radioligands for imaging the PCP binding site of the NMDA ion channel, we synthesized and characterized in vitro the candidate PCP site ligand N-(2-chloro-5-thiomethylphenyl)-N′-(3-methoxyphenyl)- N′-methylguanidine (GMOM: Ki = 5.2 ± 0.3 nM, log P = 2.34). The corresponding PET radiotracer [11C]GMOM was synthesized with a radiochemical yield of 8.4 ± 3.2% EOS and with a specific activity of 1.23 ± 0.25 Ci/μmol EOS (n = 5). The average time required for synthesis, purification and formulation was 52 ± 5 min. The final product was prepared in a sterile saline solution suitable for in vivo use. Copyright
Synthesis and in vitro evaluation of N,N'-diphenyl and N-naphthyl-N'-phenylguanidines as N-methyl-D-aspartate receptor ion-channel ligands.
Dumont, Filip,Sultana, Abida,Waterhouse, Rikki N
, p. 1583 - 1586 (2007/10/03)
A series of N,N'-diphenyl and N-naphthyl-N'-phenyl guanidine derivatives was synthesized as potential N-methyl-D-aspartate (NMDA) receptor positron emission tomography (PET) ligands. The affinity of the different compounds was determined using in vitro receptor binding assays, and their log P values were estimated using HPLC analysis. The effect of N'-3 and N'-3,5 substitution on affinity and lipophilicity was examined. The K(i) values ranged from 1.87 to 839nM, while log P values between 1.22 and 2.88 were observed.
