Reassignment of structures of the dihydro-v-tetrazines

Curtin, David Y.; Alexandrou, Nicholas

doi:10.1016/s0040-4020(01)99243-9

Cited by 47 publications

(10 citation statements)

References 10 publications

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“…Several suggestions have been made concerning the structures of the oxidation products of bisphenylhydrazones and bisbenzoylhydrazones of 1,2-diketones. These include a dihydro-l,2,3,4-tetrazine structure (von Pechman, 1897) and a bisazoolefin structure (Stolle, 1926;Grammaticakis, 1947) for the oxidation products of 1,2-diketone bisphenylhydrazones, whereas enol derivatives have been suggested as the oxidation products of bisbenzoylhydrazones of 1,2-diketones (Curtin & Alexandrou, 1963). A suggestion has also been made (Bauer et al, 1964) that certain ortho-bisazo compounds containing electron-withdrawing groups attached to one of the azo groups exist in the meso-ionic form.…”

Section: Commentmentioning

confidence: 99%

Three Cycloadducts Formed by the Reaction of Bis(phenylazo)stilbene with Acetylenic and Olefinic Dipolarophiles

Ramaiah¹,

Rath²,

George³

1998

Acta Crystallogr C

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Section: Commentmentioning

confidence: 99%

Three Cycloadducts Formed by the Reaction of Bis(phenylazo)stilbene with Acetylenic and Olefinic Dipolarophiles

Ramaiah¹,

Rath²,

George³

1998

Acta Crystallogr C

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“…Tetrazines are six-membered heterocyclic compounds, found as three structural isomers, containing a ring of four nitrogens and two carbons ( Figure 2 ). 29 , 30 The high reactivity of 1,2,4,5-tetrazine ( s -tetrazine) is attributed to the extreme electron deficiency of the nitrogen-rich ring. The fast reaction kinetics of IEDDA between 1,2,4,5-tetrazines and trans -cyclooctenes makes it the most efficient bioorthogonal reaction to date.…”

Section: Introductionmentioning

confidence: 99%

Metabolism of a Bioorthogonal PET Tracer Candidate [¹⁹F/¹⁸F]SiFA-Tetrazine in Mouse Liver Microsomes: Biotransformation Pathways and Defluorination Investigated by UHPLC-HRMS

et al. 2020

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Organofluorosilicon based 18 F-radiolabeling is an efficient method for incorporating fluorine-18 into 18 F-radiopharmaceuticals for positron emission tomography (PET) by 19 F/ 18 F isotopic exchange (IE). The first PET radiopharmaceutical, 18 F-SiFA lin -TATE, radiolabeled with a silicon-based [ 18 F]fluoride acceptor (SiFA), namely, a para-substituted di- tert -butyl[ 18 F]fluorosilylbenzene, has entered clinical trials, and is paving the way for other potential [ 18 F]SiFA-labeled radiopharmaceuticals for diagnostic use. In this study, we report the in vitro metabolism of an oxime-linked SiFA tetrazine (SiFA–Tz), a new PET-radiotracer candidate, recently evaluated for pretargeted PET imaging and macromolecule labeling. Metabolism of SiFA–Tz was studied in mouse liver microsomes (MLM) for elucidating its major biotransformation pathways. Nontargeted screening by ultrahigh performance liquid chromatography high-resolution mass spectrometry (UHPLC-HRMS) was utilized for detection of unknown metabolites. The oxime bond between the SiFA and Tz groups forms two geometric ( E / Z ) isomers, which underwent the same biotransformations, but unexpectedly with different kinetics. In total, nine proposed metabolites of SiFA–Tz from phase I and II reactions were detected, five of which were defluorinated in MLMs, elucidating the metabolic pathway leading to previously reported defluorination of [ 18 F]SiFA–Tz in vivo . Based on the HRMS studies a biotransformation pathway is proposed: hydroxylation (+O) to tert -butyl group adjacent to the silicon, followed by oxidative defluorination (+OH/-F) cleaving the fluorine off the silicon. Interestingly, eight proposed metabolites of a reduced dihydrotetrazine analogue, SiFA–H 2 Tz, from phase I and II reactions were additionally detected. To the best of our knowledge, this is the first reported comprehensive investigation of enzyme mediated metabolic pathway of tetrazines and para-substituted di- tert -butylfluorosilylbenzene fluoride acceptors, providing novel structural information on the biotransformation and fragmentation patterns of radiotracers bearing these structural motifs. By investigating the metabolism preceding defluorination, structurally optimized new SiFA compounds can be designed for expanding the portfolio of efficient 19 F/ 18 F isotopic exchange labeling probes for PET imaging.

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“…for the preparation of condensed 1,2,3-triazolo heterocycles, such as the 4H-3,6-diaryl [ 1,2,3]triazolo[ 1,5-d ] [ 1,3,4]oxadiazines? We have found that 13C NMR spectroscopy can be used as a rapid and easy method for distinguishing between the two possible isomers, and now report our results.…”

Section: Introductionmentioning

confidence: 99%

¹³C NMR Spectra of 1‐Amino‐1,2,3‐triazole Derivatives. 2—Identification of 4,5‐Unsymetrically Substituted 1‐(N,N‐Diaroyl)amino‐1,2,3‐triazotes

Rodios¹

1985

Magnetic Reson in Chemistry

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The 13C NMR spectra of some I-(N,Ndiaroyllami no-I ,2,3-triazole derivatives are reported. The shifts of the methyl carbons attached to the triazole ring and those of C-4 and C-5 of the ring were used to distinguish between 4.5-unsymmetrically substituted derivatives. The location of a methyl group on the 4-or 5-position of the ring can be also deduced from the ' J CH, value. A complete assignment of the aroyl carbons of the imide moiety is given.

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Reassignment of structures of the dihydro-v-tetrazines

Cited by 47 publications

References 10 publications

Three Cycloadducts Formed by the Reaction of Bis(phenylazo)stilbene with Acetylenic and Olefinic Dipolarophiles

Three Cycloadducts Formed by the Reaction of Bis(phenylazo)stilbene with Acetylenic and Olefinic Dipolarophiles

Metabolism of a Bioorthogonal PET Tracer Candidate [¹⁹F/¹⁸F]SiFA-Tetrazine in Mouse Liver Microsomes: Biotransformation Pathways and Defluorination Investigated by UHPLC-HRMS

¹³C NMR Spectra of 1‐Amino‐1,2,3‐triazole Derivatives. 2—Identification of 4,5‐Unsymetrically Substituted 1‐(N,N‐Diaroyl)amino‐1,2,3‐triazotes

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Reassignment of structures of the dihydro-v-tetrazines

Cited by 47 publications

References 10 publications

Three Cycloadducts Formed by the Reaction of Bis(phenylazo)stilbene with Acetylenic and Olefinic Dipolarophiles

Three Cycloadducts Formed by the Reaction of Bis(phenylazo)stilbene with Acetylenic and Olefinic Dipolarophiles

Metabolism of a Bioorthogonal PET Tracer Candidate [19F/18F]SiFA-Tetrazine in Mouse Liver Microsomes: Biotransformation Pathways and Defluorination Investigated by UHPLC-HRMS

13C NMR Spectra of 1‐Amino‐1,2,3‐triazole Derivatives. 2—Identification of 4,5‐Unsymetrically Substituted 1‐(N,N‐Diaroyl)amino‐1,2,3‐triazotes

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Metabolism of a Bioorthogonal PET Tracer Candidate [¹⁹F/¹⁸F]SiFA-Tetrazine in Mouse Liver Microsomes: Biotransformation Pathways and Defluorination Investigated by UHPLC-HRMS

¹³C NMR Spectra of 1‐Amino‐1,2,3‐triazole Derivatives. 2—Identification of 4,5‐Unsymetrically Substituted 1‐(N,N‐Diaroyl)amino‐1,2,3‐triazotes