Synthesis and evaluation of 6-[11C]methoxy-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-1,2- benzisoxazole as an in vivo radioligand for acetylcholinesterase
| Autor: | Clive Brown-Proctor, Scott E. Snyder, Michael R. Kilbourn, Phillip S. Sherman |
|---|---|
| Rok vydání: | 1999 |
| Předmět: |
Cancer Research
Chemistry Stereochemistry Benzisoxazole Brain Isoxazoles Desmethyl Ligand (biochemistry) Chemical synthesis Acetylcholinesterase chemistry.chemical_compound Mice Piperidines In vivo Alzheimer Disease Radioligand Molecular Medicine Animals Radiology Nuclear Medicine and imaging Female Carbon Radioisotopes Macaca nemestrina Methyl trifluoromethanesulfonate Tomography Emission-Computed |
| Zdroj: | Nuclear medicine and biology. 26(1) |
| ISSN: | 0969-8051 |
| Popis: | ABSTRACT. 6-Methoxy-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-1,2-benzisoxazole is a high affinity (Ki = 8.2 nM) reversible inhibitor of acetylcholinesterase (AChE). The carbon-11 labeled form was prepared in high (>97%) radiochemical purity and with specific activities of 37 ± 20 GBq/μmol at end of synthesis, by the alkylation of the desmethyl precursor with [11C]methyl trifluoromethanesulfonate in N,N-dimethylformamide at room temperature. In vivo studies in mice demonstrated good blood brain permeability but essentially uniform regional brain distribution. Thus, despite in vitro and in vivo activity as an AChE inhibitor, 6-[11C]methoxy-3-[2-[1-(phenylmethyl)-4-piperidinyl]ethyl]-1,2-benzisoxazole does not appear to be a good candidate for in vivo imaging studies of AChE in the mammalian brain. |
| Databáze: | OpenAIRE |
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