Journal Article

FZJ-2016-06731

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Synthesis of a Potent Aminopyridine-Based nNOS-Inhibitor by Two Recent No-Carrier-Added $^{18}$F-Labelling Methods

Drerup, C. ; Ermert, J. (Corresponding author)FZJ* ; Coenen, H. H.FZJ*

2016
MDPI75390 Basel

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Please use a persistent id in citations: http://hdl.handle.net/2128/13129  doi:10.3390/molecules21091160

Abstract: Nitric oxide (NO), an important multifunctional signaling molecule, is produced by threeisoforms of NO-synthase (NOS) and has been associated with neurodegenerative disorders. Selectiveinhibitors of the subtypes iNOS (inducible) or nNOS (neuronal) are of great interest for decodingneurodestructive key factors, and 18F-labelled analogues would allow investigating the NOS-functionby molecular imaging with positron emission tomography. Especially, the highly selective nNOSinhibitor 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 preparationof the 18F-labelled nNOS-Inhibitor [18F]10 a “build-up” radiosynthesis was developed based on acorresponding iodonium ylide as labelling precursor. The such activated phenethyl group of thecompound was efficiently and regioselectively labelled with n.c.a. [18F]fluoride in 79% radiochemicalyield (RCY). After conversion by reductive amination and microwave assisted displacement of theprotecting 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 wassynthesized and successfully used in a newer, copper(II) mediated n.c.a. 18F-fluoro-deboroniationreaction, achieving the same total RCY. Thus, both methods proved comparatively suited to providethe highly selective NOS-inhibitor [18F]10 as probe for preclinical in vivo studies.

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Contributing Institute(s):

1. Nuklearchemie (INM-5)

Research Program(s):

1. 573 - Neuroimaging (POF3-573) (POF3-573)

Appears in the scientific report 2016

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Database coverage:
; ; ; ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; IF < 5 ; JCR ; NCBI Molecular Biology Database ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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