Synthesis and Stability Evaluation of New HYNIC Derivatives as Ligands for Technetium-99m

Joyard, Yoann; Bischoff, Laurent; Levacher, Vincent; Papamicaël, Cyril; Véra, Pierre; Bohn, Pierre

doi:10.2174/15701786113106660087

Cited by 3 publications

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“…The synthesis of 2‐nitro‐1‐(prop‐2‐yn‐1‐yl)‐1 H ‐imidazole ( 11 ), described by Joyard and coworkers, occurs through the alkylation of 2‐nitroimidazole ( 18 ) via bimolecular nucleophilic substitution using propargyl iodide generated in situ from propargyl bromide . 18‐Crown‐6 was used as a phase transfer catalyst, and potassium carbonate was used as the base in dimethylformamide (DMF) at room temperature for 1 hr (Scheme ).…”

Section: Resultsmentioning

confidence: 99%

“…Intermediate 11 was obtained as yellow oil in 86% yield, and its chemical structure was confirmed by liquid chromatography‐mass spectrometry (LC‐MS) and infrared (IR) and 1 H and 13 C nuclear magnetic resonance (NMR) spectroscopies. The results of the analyses were compared with the literature data as this intermediate is already described …”

Section: Resultsmentioning

confidence: 99%

“…The synthesis of 2‐nitro‐1‐(prop‐2‐yn‐1‐yl)‐1 H ‐imidazole ( 11 ) was described in the literature . In this work, a mixture of 2‐nitroimidazole ( 18 ) (0.0088 mol, 1 g), anhydrous potassium carbonate (1.9 mol, 2.32 g), sodium iodide (0.32 mol, 0.42 g), 3‐bromoprop‐1‐yne (1.6 mol, 1.70 g) and 18‐crown‐6 (0.0088 mol, 0.094 g) in DMF anhydrous (30 ml) was combined and stirred at room temperature for 1 hr.…”

Section: Methodsmentioning

confidence: 99%

“…The literature described many methodologies for the synthesis of 1,2,3‐triazole ring, using the 2‐nitro‐1‐(prop‐2‐yn‐1‐yl)‐1 H ‐imidazole ( 11 ) as starting materials . In this work, these compounds were prepared through the reaction of azides 12–17 (2.2 mmol) and 2‐nitro‐1‐(prop‐2‐yn‐1‐yl)‐1 H ‐imidazole ( 11 ) (2.8 mmol), sodium ascorbate (0.22 mmol), copper sulphate (0.13 mmol) and 20 ml of a mixture of t ‐butanol:water (1:1).…”

Section: Methodsmentioning

confidence: 99%

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New 1,2,3‐triazole‐based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations

et al. 2018

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Chagas disease has spread throughout the world mainly because of the migration of infected individuals. In Brazil, only benznidazole (Bnz) is used; however, it is toxic and not active in the chronic phase, and cases of resistance are described. This work aimed at the synthesis and the trypanocidal evaluation in vitro and in vivo of six new Bnz analogues (3-8). They were designed by exploring the bioisosteric substitution between the amide group contained in Bnz and the 1,2,3-triazole ring. All the compounds were synthesized in good yields. With the exception of compound 7, the in vitro biological evaluation shows that all Bnz analogues were active against the amastigote form, whereas only compounds 3, 4, 5, and 8 were active against trypomastigote. Compounds 4 and 5 showed the most promising activities in vitro against the form of trypomastigote, being more active than Bnz. In vivo evaluation of compounds, 3-8 showed lower potency and higher toxicity than Bnz. Although the 1,2,3-triazole ring has been described in the literature as an amide bioisostere, its substitution here has reduced the activity of the compounds and made them more toxic. Thus, further molecular optimization could provide novel therapeutic agents for Chagas' disease.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

New 1,2,3‐triazole‐based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations

et al. 2018

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“…However, the free hydrazine group of HYNIC is not stable in an aqueous solution and can react with other groups. Joyard et al [ 40 ] prepared two 2-nitroimidazole HYNIC derivatives radiolabeled with technetium-99m, but decomposition of the ligands occurred, and they proposed a self-redox process between 2-nitroimidazole and HYNIC ligands. In addition, the hydrazine group can react with aldehydes and ketones, which may leach out from various rubber and plastic materials, to form various hydrazone impurities [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

Preparation and Bioevaluation of Novel 99mTc-Labeled Complexes with a 2-Nitroimidazole HYNIC Derivative for Imaging Tumor Hypoxia

et al. 2021

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To develop novel 99mTc-labeled single-photon emission computed tomography (SPECT) radiotracers for imaging hypoxia, a novel HYNICNM ligand (6-hydrazinonicotinamide (HYNIC) 2-nitroimidazole derivative) was designed and synthesized. It was radiolabeled with technetium-99m using tricine/trisodium triphenylphosphine-3,3′,3′′-trisulfonate (TPPTS), tricine/sodium triphenylphosphine-3-monosulfonate (TPPMS) and tricine as co-ligands to obtain [99mTc]Tc-tricine-TPPTS-HYNICNM, [99mTc]Tc-tricine-TPPMS-HYNICNM, and [99mTc]Tc-(tricine)2-HYNICNM, respectively. The three technetium-99m complexes were radiolabeled in one step with a high yield (95%) and had good stability in saline and mouse serum. In vitro cellular uptake results showed that these complexes exhibited good hypoxic selectivity. The partition coefficient indicated that they were good hydrophilic complexes, and [99mTc]Tc-tricine-TPPTS-HYNICNM displayed the highest hydrophilicity (-3.02 ± 0.08). The biodistribution in mice bearing S180 tumors showed that [99mTc]Tc-tricine-TPPTS-HYNICNM exhibited higher tumor uptake (1.05 ± 0.27% IA/g); more rapid clearance from the liver, blood, muscle, and other non-target organs; and a higher tumor/non-target ratio, especially for the tumor/liver ratio (1.95), than [99mTc]Tc-tricine-TPPMS-HYNICNM and [99mTc]Tc-(tricine)2-HYNICNM. The results of single-photon emission computed tomography (SPECT) imaging studies of [99mTc]Tc-tricine-TPPTS-HYNICNM were in accordance with the biodistribution results, which suggested that [99mTc]Tc-tricine-TPPTS-HYNICNM is a promising agent for imaging tumor hypoxia.

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Convenient, DBU-promoted anti-Markovnikov hydration of 2-methyl-1-(3-arylprop-2-yn-1-yl)-1H-imidazoles in wet NMP

Lukin

Nichugovskaya

Vinogradova

et al. 2023

Mendeleev Communications

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Synthesis and Stability Evaluation of New HYNIC Derivatives as Ligands for Technetium-99m

Cited by 3 publications

References 0 publications

New 1,2,3‐triazole‐based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations

New 1,2,3‐triazole‐based analogues of benznidazole for use against Trypanosoma cruzi infection: In vitro and in vivo evaluations

Preparation and Bioevaluation of Novel 99mTc-Labeled Complexes with a 2-Nitroimidazole HYNIC Derivative for Imaging Tumor Hypoxia

Convenient, DBU-promoted anti-Markovnikov hydration of 2-methyl-1-(3-arylprop-2-yn-1-yl)-1H-imidazoles in wet NMP

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