کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1360551 981439 2009 12 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Synthesis of spirocyclic σ1 receptor ligands as potential PET radiotracers, structure–affinity relationships and in vitro metabolic stability
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
Synthesis of spirocyclic σ1 receptor ligands as potential PET radiotracers, structure–affinity relationships and in vitro metabolic stability
چکیده انگلیسی

Several 3H-spiro[[2]benzofuran-1,4′-piperidines] bearing a p-fluorobenzyl residue at the N-atom and various substituents in position 3 of the benzofuran system were synthesized. The crucial reaction steps are the addition of a lithiated benzaldehyde derivative to the p-fluorobenzylpiperidone 5 and the BF3·OEt2 catalyzed substitution of the methoxy group of 2a by various nucleophiles. Structure–affinity relationship studies revealed that compounds with two protons (2d), a methoxy group (2a), and a cyano group (2e) in position 3 possess subnanomolar σ1 affinity (Ki = 0.18 nM, 0.79 nM, 0.86 nM) and high selectivity against the σ2 subtype. The metabolites of 2a, 2d, and 2e, which were formed upon incubation with rat liver microsomes, were identified. Additionally, the rate of metabolic degradation of 2a, 2d, and 2e was determined and compared with the degradation rate of the non-fluorinated spirocyclic compound 1. For the synthesis of the potential PET tracers [18F]2a and [18F]2e two different radiosynthetic approaches were followed.

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ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic & Medicinal Chemistry - Volume 17, Issue 10, 15 May 2009, Pages 3630–3641
نویسندگان
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