Efficient synthesis and first regioselective C-6 direct arylation of imidazo[2,1-c][1,2,4]triazine scaffold and their evaluation in H2O2-induced oxidative stress

Loubidi, Mohammed; Jouha, Jabrane; Tber, Zahira; Khouili, Mostafà; Suzenet, Franck; Akssira, Mohamed; Erdoğan, Mümin Alper; Köse, Faruk; Dağcı, Taner; Armağan, Güliz; Saso, Luciano; Guillaumet, Gérald

doi:10.1016/j.ejmech.2017.12.081

Cited by 15 publications

(5 citation statements)

References 45 publications

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“…Imidazopyrimidine and imidazopyridazine cores were obtained from the cyclization of the corresponding 2-aminopyrimidine and 3-aminopyridazin with the nitrophenyl-α-bromoketone 58 (Scheme ). − The nitro derivatives 59 and 60 were reduced to the corresponding aromatic amines 61 and 62 with tin(II) chloride under acidic conditions. The latter were then coupled with either trichloroacetyl dibromopyrrole 14a in Et 3 N or with the acyl chloride prepared in situ to afford 63 and 64 , respectively …”

Section: Resultsmentioning

confidence: 99%

From Synthetic Simplified Marine Metabolite Analogues to New Selective Allosteric Inhibitor of Aurora B Kinase

et al. 2021

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Significant inhibition of Aurora B was achieved by the synthesis of simplified fragments of benzosceptrins and oroidin belonging to the marine pyrrole-2-aminoimidazoles metabolites isolated from sponges. Evaluation of kinase inhibition enabled the discovery of a synthetically accessible rigid acetylenic structural analog EL-228 (1), whose structure could be optimized into the potent CJ2-150 (37. Here we present the synthesis of new inhibitors of Aurora B kinase which is an important target for cancer therapy through mitosis regulation. The biologically oriented synthesis yielded several nanomolar inhibitors. The optimized compound CJ2-150 (37) showed a non-ATP competitive allosteric mode of action in a mixed-type inhibition for Aurora B kinase. Molecular docking identified a probable binding mode in the allosteric site "F" and highlighted the key interactions with the protein. We describe the improvement of the inhibitory potency and specificity of the novel scaffold as well as the characterization of the mechanism of action.

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Section: Resultsmentioning

confidence: 99%

From Synthetic Simplified Marine Metabolite Analogues to New Selective Allosteric Inhibitor of Aurora B Kinase

et al. 2021

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“…These examples involve reactions of 2‐aminoazines ( 1 b , 1 d , 1 e , and 1 f ) and α ‐halocarbonyl compounds 36 – 39 in protic (methanol, ethanol, ethylene glycol, and water) or aprotic ( N,N ‐dimethyl formamide, N,N ‐dimethylacetamide,1,2‐dimethoxyethane, and acetone) solvents. The final bicyclic compounds include imidazo[1,2‐b]pyridazines 40 and 41 , [36,37] imidazo[1,2‐a]pyrazines 42 , [38,29] imidazo[1,2‐a]pyrimidines 43 a – 43 b , [40,41] and imidazo[1,2‐a][1,3,5]triazine 43 c [42] …”

Section: Synthetic Methods For Fused Imidazole and Pyrimidinonementioning

confidence: 99%

“…The recent examples of fused imidazoles synthesized from α-halocarbonyl compounds are presented in Figure 4. [36,37] imidazo[1,2a]pyrazines 42, [38,29] imidazo[1,2-a]pyrimidines 43 a-43 b, [40,41] and imidazo[1,2-a][1,3,5]triazine 43 c. [42] Variations of the halide compounds have also been investigated. Peese et al [43] developed a protocol for the synthesis of electron-deficient imidazopyridine 45 by heating 2aminopyridine (1 g, 1.0 equiv.)…”

Section: Reactions With α-Halo Ketones or Aldehydesmentioning

confidence: 99%

Synthesis of Fused Imidazoles and Pyrimidinones from 2‐Aminoazines

Wang,

Jiang,

Liu

et al. 2024

Asian J Org Chem

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Fused imidazole and pyrimidine heterocycles represent two important classes of organic compounds. Numerous synthetic methods have been developed for the synthesis of these compounds due to their diverse biological activities and potential pharmaceutical applications. This review provides a comprehensive assessment of the cutting‐edge methods used in the synthesis of fused heterocycles from pyridin‐2‐amines and their aza derivatives involving reaction with 1,3‐dicarbonyl compounds or α‐halo carbonyl compounds. In addition, the Groebke‐Blackburn‐Bienaymé (GBB) reaction, metal‐mediated reactions and other related reaction systems have been considered. We summarize the pertinent literature on related synthetic methods in the period 2020 to 2023. The analysis provided can inform future developments directed at new cost‐effective approaches to the synthesis of fused imidazole and fused pyrimidine analogues.

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“…Molecules 4a–c (Figure 2) were found to protect SH‐SY5Y cells from H 2 O 2 ‐induced toxicity by increasing the Bcl‐2/Bax ratio, regulating the PI3‐K/Akt cascade, and inhibiting the ERK pathway. [ 49 ]…”

Section: Triazines In Alzheimer's Diseasementioning

confidence: 99%

“…[48] F I G U R E 2 Molecules containing triazine with single therapeutic potential in Alzheimer's disease toxicity by increasing the Bcl-2/Bax ratio, regulating the PI3-K/Akt cascade, and inhibiting the ERK pathway. [49] A series of novel piperazine tethered biphenyl-3-oxo-1,2,4triazine derivatives were designed, and synthesized by Tripathi et al…”

Section: Triazine-containing Molecules Modulating Single Target In Admentioning

confidence: 99%

Potential of triazines in Alzheimer's disease: A versatile privileged scaffold

Gharat

Prabhu

Khambete

2022

Archiv der Pharmazie

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Triazines are six-membered privileged scaffolds that have been explored in drug discovery programs owing to their stability in biological media and robust reactivity.Their unique chemical properties have led to the exploration of the triazinecontaining molecules for multifaceted disorders like Alzheimer's disease (AD). The pathology of AD involves the interplay of multiple biochemical events such as amyloid beta-aggregation, formation of reactive oxygen species, cholinergic degradation, and metal ion dysregulation. The growing incidence of AD, coupled with the limited availability of efficacious medicines, necessitates the identification of newer therapeutic approaches. Privileged scaffolds like triazines with the potential for multiple biological effects offer excellent alternatives to the treatment of multifactorial AD. The present review describes numerous triazine-containing molecules capable of modulating single as well as multiple pathological factors involved in AD.The analysis of structural features of these molecules can provide useful insights for developing newer therapies.

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Efficient synthesis and first regioselective C-6 direct arylation of imidazo[2,1-c][1,2,4]triazine scaffold and their evaluation in H2O2-induced oxidative stress

Cited by 15 publications

References 45 publications

From Synthetic Simplified Marine Metabolite Analogues to New Selective Allosteric Inhibitor of Aurora B Kinase

From Synthetic Simplified Marine Metabolite Analogues to New Selective Allosteric Inhibitor of Aurora B Kinase

Synthesis of Fused Imidazoles and Pyrimidinones from 2‐Aminoazines

Potential of triazines in Alzheimer's disease: A versatile privileged scaffold

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