Synthesis and evaluation of indolinyl- and indolylphenylacetylenes as PET imaging agents for β-amyloid plaques
| Autor: | Catherine Hou, Mei-Ping Kung, Wei Zhang, Daniel Skovronsky, Rajesh Manchandra, Shunichi Oya, Zhi-Ping Zhuang, Hank F. Kung, Wenchao Qu, Seok-Rye Choi |
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| Rok vydání: | 2008 |
| Předmět: |
Indoles
Stereochemistry Clinical Biochemistry Contrast Media Pharmaceutical Science Plaque Amyloid Ether Blood–brain barrier Biochemistry Chemical synthesis Article Mice chemistry.chemical_compound Alzheimer Disease Drug Discovery medicine Radioligand Animals Humans Molecular Biology Indole test Amyloid beta-Peptides Acetylene Organic Chemistry Brain medicine.anatomical_structure Phenylacetylene chemistry Positron-Emission Tomography Indoline Alkoxy group Molecular Medicine |
| Zdroj: | Bioorganic & Medicinal Chemistry Letters. 18:4823-4827 |
| ISSN: | 0960-894X |
| Popis: | Two new phenylacetylene derivatives, 5-((4-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)phenyl)ethynyl)indoline 8 and 5-((4-(2-(2-(2-fluoroethoxy)ethoxy)ethoxy)phenyl)ethynyl)-1 H -indole 14 , targeting β-amyloid (Aβ) plaques have been prepared. In vitro binding carried out in tissue homogenates prepared from postmortem AD brains with [ 125 I]IMPY (6-iodo-2-(4′-dimethylamino-)phenyl-imidazo[1,2- a ]pyridine) as the radioligand indicated good binding affinities ( K i = 4.0 and 1.5 nM for 8 and 14 , respectively). Brain penetration of the corresponding radiofluorinated ligands, evaluated in the normal mice, showed good initial brain penetration (4.50 and 2.43% ID/g (injected dose/gram) for [ 18 F] 8 and [ 18 F] 14 at 2 min after injection) with moderate to low washout rates from the brain (1.71% ID/g at 2 h and 2.10% ID/g at 3 h, respectively). Autoradiography and homogenate binding studies demonstrated the high specific binding of [ 18 F] 14 to the Aβ plaques; however, [ 18 F] 8 showed low specific binding. These preliminary results identified that indolylphenylacetylene, 14 , may be a good lead for further structural modification to develop a useful Aβ plaque imaging agent. |
| Databáze: | OpenAIRE |
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