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Molecules 2016, 21(9), 1160;

Synthesis of a Potent Aminopyridine-Based nNOS-Inhibitor by Two Recent No-Carrier-Added 18F-Labelling Methods

Institut für Neurowissenschaften und Medizin, INM-5: Nuklearchemie, Forschungszentrum Jülich, 52425 Jülich, Germany
Author to whom correspondence should be addressed.
Academic Editor: Michael Gütschow
Received: 3 August 2016 / Revised: 24 August 2016 / Accepted: 25 August 2016 / Published: 1 September 2016
(This article belongs to the Section Medicinal Chemistry)
Full-Text   |   PDF [5737 KB, uploaded 1 September 2016]   |  


Nitric oxide (NO), an important multifunctional signaling molecule, is produced by three isoforms of NO-synthase (NOS) and has been associated with neurodegenerative disorders. Selective inhibitors of the subtypes iNOS (inducible) or nNOS (neuronal) are of great interest for decoding neurodestructive key factors, and 18F-labelled analogues would allow investigating the NOS-function by molecular imaging with positron emission tomography. Especially, the highly selective nNOS inhibitor 6-((3-((3-fluorophenethylamino)methyl)phenoxy)methyl)-4-methylpyridin-2-amine (10) lends itself as suitable compound to be 18F-labelled in no-carrier-added (n.c.a.) form. For preparation of the 18F-labelled nNOS-Inhibitor [18F]10 a “build-up” radiosynthesis was developed based on a corresponding iodonium ylide as labelling precursor. The such activated phenethyl group of the compound was efficiently and regioselectively labelled with n.c.a. [18F]fluoride in 79% radiochemical yield (RCY). After conversion by reductive amination and microwave assisted displacement of the protecting groups, the desired nNOS-inhibitor was obtained in about 15% total RCY. Alternatively, for a simplified “late-stage” 18F-labelling procedure a corresponding boronic ester precursor was synthesized and successfully used in a newer, copper(II) mediated n.c.a. 18F-fluoro-deboroniation reaction, achieving the same total RCY. Thus, both methods proved comparatively suited to provide the highly selective NOS-inhibitor [18F]10 as probe for preclinical in vivo studies. View Full-Text
Keywords: radiofluorination; radiopharmaceuticals; nNOS-inhibitor; iodonium ylides; copper-mediated labelling radiofluorination; radiopharmaceuticals; nNOS-inhibitor; iodonium ylides; copper-mediated labelling

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Drerup, C.; Ermert, J.; Coenen, H.H. Synthesis of a Potent Aminopyridine-Based nNOS-Inhibitor by Two Recent No-Carrier-Added 18F-Labelling Methods. Molecules 2016, 21, 1160.

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