233766-72-8

Upstream product

• 16867-03-1 2-amino-3-hydroxypyridine 
• 50-00-0 formaldehyd 
• 506-59-2 N,N-dimethylammonium chloride 
• 174669-74-0 2-fluoro-3-hydroxypyridine 

Downstream Products

• 233766-75-1 (3-<2(S)-N-(tert-butoxycarbonyl)-2-azetidinylmethoxy>pyridin-2-yl)trimethylammonium trifluoromethanesulfonate 

Relevant academic research and scientific papers

[18F]FPyZIDE: A versatile prosthetic reagent for the fluorine-18 radiolabeling of biologics via copper-catalyzed or strain-promoted alkyne-azide cycloadditions

Methods for the radiolabeling of biologics with fluorine-18 have been of interest for several decades. A common approach consists in the preparation of a prosthetic reagent, a small molecule bearing a fluorine-18 that is conjugated with the macromolecule to an appropriate function. Click chemistry, and more particularly cycloadditions, is an interesting approach to radiolabel molecules thanks to mild reaction conditions, high yields, low by-products formation, and strong orthogonality. Moreover, the chemical functions involved in the cycloaddition reaction are stable in the drastic radiofluorination conditions, thus allowing a simple radiosynthetic route to prepare the prosthetic reagent. We report herein the radiosynthesis of 18F-FPyZIDE, a pyridine-based azide-bearing prosthetic reagent. We exemplified its conjugation via copper-catalyzed cycloaddition (CuAAC) and strain-promoted cycloaddition (SPAAC) with several terminal alkyne or strained alkyne model compounds.

A novel 2-cyanobenzothiazole-based 18F prosthetic group for conjugation to 1,2-aminothiol-bearing targeting vectors

In a bid to find an efficient means to radiolabel biomolecules under mild conditions for PET imaging, a bifunctional 18F prosthetic molecule has been developed. The compound, dubbed [18F]FPyPEGCBT, consists of a 2-substituted pyridine moiety for [18F]F- incorporation and a 2-cyanobenzothiazole moiety for coupling to terminal cysteine residues. The two functionalities are separated by a mini-PEG chain. [18F]FPyPEGCBT could be prepared from its corresponding 2-trimethylammonium triflate precursor (100 °C, 15 min, MeCN) in preparative yields of 11% ± 2 (decay corrected, n = 3) after HPLC purification. However, because the primary radiochemical impurity of the fluorination reaction will not interact with 1,2-aminothiol functionalities, the 18F prosthetic could be prepared for bioconjugation reactions by way of partial purification on a molecularly imprinted polymer solid-phase extraction cartridge. [18F]FPyPEGCBT was used to 18F-label a cyclo-(RGDfK) analogue which was modified with a terminal cysteine residue (TCEP·HCl, DIPEA, 30 min, 43°C, DMF). Final decay-corrected yields of 18F peptide were 7% ± 1 (n = 9) from end-of-bombardment. This novel integrin-imaging agent is currently being studied in murine models of cancer. We argue that [18F]FPyPEGCBT holds significant promise owing to its straightforward preparation, 'click'-like ease of use, and hydrophilic character. Indeed, the water-tolerant radio-bioconjugation protocol reported herein requires only one HPLC step for 18F peptide purification and can be carried out remotely using a single automated synthesis unit over 124-132 min.

Radiosynthesis and bioconjugation of [18F]FPy5yne, a prosthetic group for the18F labeling of bioactive peptides

A new 18F-based prosthetic group has been prepared for the labeling of azide-modified peptides for use in PET imaging. 2-[ 18F]fluoro-3-(hex-5-ynyloxy)pyridine ([18F]FPy5yne, [ 18F]-1) was prepared via efficient nucleophilic heteroaromatic substitution of either the corresponding 2-nitro (2) or 2-trimethylammonium trifluoromethanesulfonate pyridine (3). Best radiochemical yield of [ 18F]FPy5yne from 2 was 91% by radioTLC (15 min, 110°C, DMSO). From 3, best radiochemical yield by radioTLC was 93% (15 min, 110°C, MeCN). HPLC-purified [18F]FPy5yne was ligated to model peptide N 3-(CH2)4-CO-YK-RI-OH by way of Cu I-mediated Huisgen [3+2] cycloaddition in the presence of copper-stabilizing ligand tris(benzyl-triazolylmethyl) amine (TBTA) and N,N-diisopropylethylamine (DIEA). Bioconjugate radiochemical yields were obtained in average yields of 89%78.6% (n = 4), as judged by radioHPLC. Best non-decay-corrected, collected radiochemical yield of modified peptide from end-of-bombardment was 5.8% (18.7% decay-corrected), with a total preparation time of 160 min from start of synthesis. Copyright

[18F]FPyKYNE, a fluoropyridine-based alkyne reagent designed for the fluorine-18 labelling of macromolecules using click chemistry

FPyKYNE (2-fluoro-3-pent-4-yn-1-yloxypyridine) is a novel fluoropyridine-based structure, designed for the fluorine-18 labelling of macromolecules using copper-catalysed Huisgen 1,3-dipolar cycloaddition (click chemistry). FPyKYNE (non-labelled as reference), as well as the 2-bromo, 2-nitro and 2-trimethylammonium analogues (as precursors for labelling with fluorine-18), was synthesized in 44, 95, 60 and 41%, respectively, from commercially available 5-chloropent-1-yne and the appropriate 2-substituted-3-hydroxypyridines. [18F]FPyKYNE was synthesized in one single radiochemical step by reaction of no-carrier-added K[ 18F]F-Kryptofix 222 (DMSO, 165°C, 3-5 min) followed by C-18 SepPak cartridge pre-purification and finally semi-preparative HPLC purification on a Hewlett Packard SiO2 Zorbax Rx-SIL. Using the 2-nitropyridine or the pyridin-2-yltrimethylammonium trifluoromethanesulphonate precursor for labelling (30 and 10 μmol, respectively), incorporation yields up to 90% were observed and 7.0-8.9 GBq (190-240 mCi) of [18F]FPyKYNE ([18F]-1) could be isolated within 60-70 min (HPLC purification included), starting from a 37.0 GBq (1.0 Ci) [18F]fluoride batch (overall decay-corrected and isolated yields: 30-35%). Copyright

Synthesis and nicotinic acetylcholine receptor in vivo binding properties of 2-fluoro-3-[2(S)-2-azetidinylmethoxy]pyridine: A new positron emission tomography ligand for nicotinic receptors

The lead compound of a new series of 3-pyridyl ethers, the azetidine derivative A-85380 (3[(S)-2-azetidinylmethoxy]pyridine), is a potent and selective ligand for the human α4β2 nicotinic acetylcholine receptor (nAChR) subtype. In vitro, the fluoro derivative of A-85380 (2-fluoro-3[(S)- 2-azetidinylmethoxy]pyridine or F-A-85380) competitively displaced [3H]cytisine or [3H]epibatidine with K(i) values of 48 and 46 pM, respectively. F-A-85380 has been labeled with the positron emitter fluorine- 18(t( 1/2 ) (half-life) = 110 min) by no-carrier-added nucleophilic aromatic substitution by K[18F]F-K222 complex with (3-[2(S)-N-(tert- butoxycarbonyl)-2-azetidinylmethoxy]pyridin-2-yl)trimethylammonium trifluoromethanesulfonate as a highly efficient labeling precursor, followed by TFA removal of the Boc protective group. The total synthesis time was 50- 53 min from the end of cyclotron fluorine-18 production (EOB). Radiochemical yields, with respect to initial [18F]fluoride ion radioactivity, were 68- 72% (decay-corrected) and 49-52% (non-decay-corrected), and the specific radioactivities at EOB were 4-7 Ci/μmol (148-259 GBq/μmol). In vivo characterization of [18F]F-A-85380 showed promising properties for PET imaging of central nAChRs. This compound does not bind in vivo to α7 nicotinic or 5HT3 receptors. Moreover, its cerebral uptake can be modulated by the synaptic concentration of the endogenous ligand acetylcholine. The preliminary PET experiments in baboons with [18F]F-A-85380 show an accumulation of the radiotracer in the brain within 60 min. In the thalamus, a nAChR-rich area, uptake of radioactivity reached a maximum at 60 min (4% I.D./100 mL of tissue). [18F]F-A-85380 appears to be a suitable radioligand for brain imaging nAChRs with PET.