Discovery of thinopyrimidine-triazole conjugates as c-Met targeting and apoptosis inducing agents

Wang, Linxiao; Xu, Shan; Liu, Xiaobo; Chen, Xiuying; Xiong, Hehua; Hou, Shanshan; Zou, Wen-Sheng; Tang, Qidong; Zheng, Pengwu; Zhu, Wufu

doi:10.1016/j.bioorg.2018.01.037

Cited by 31 publications

(16 citation statements)

References 16 publications

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“…6) was discovered as a c-Met-targeting and apoptosis-inducing agent among the synthesised thiopyrimidine-triazole conjugates. 76 This lead compound demonstrated 3.7-5.4-fold greater activity than the positive control drug, foretinib, did toward the MCF-7, HepG2, and A549 cell lines with the IC 50 values of 1.1, 0.5, and 0.9 µM, respectively. Furthermore, enzyme-based experiments showed that 37 selectively inhibited c-Met, with an IC 50 of 16 nM, which was similar to that of foretinib (14 nM).…”

Section: Diverse 123-triazole-containing Heterocyclic Hybridsmentioning

confidence: 85%

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

Bozorov

Zhao

Aisa

2019

Bioorganic & Medicinal Chemistry

579

289

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A B S T R A C TThe 1,2,3-triazole ring is a major pharmacophore system among nitrogen-containing heterocycles. These fivemembered heterocyclic motifs with three nitrogen heteroatoms can be prepared easily using 'click' chemistry with copper-or ruthenium-catalysed azide-alkyne cycloaddition reactions. Recently, the 'linker' property of 1,2,3-triazoles was demonstrated, and a novel class of 1,2,3-triazole-containing hybrids and conjugates was synthesised and evaluated as lead compounds for diverse biological targets. These lead compounds have been demonstrated as anticancer, antimicrobial, anti-tubercular, antiviral, antidiabetic, antimalarial, anti-leishmanial, and neuroprotective agents. The present review summarises advances in lead compounds of 1,2,3-triazolecontaining hybrids, conjugates, and their related heterocycles in medicinal chemistry published in 2018. This review will be useful to scientists in research fields of organic synthesis, medicinal chemistry, phytochemistry, and pharmacology. Chemistry: synthesis and properties of the 1,2,3-triazolesThe general synthetic route of 1,2,3-triazoles using click chemistry is described in Scheme 1A. The most popular route to 1,2,3-triazoles is Cu(I)-catalysed Huisgen 1,3-dipolar cycloaddition, which is the https://doi.

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Section: Diverse 123-triazole-containing Heterocyclic Hybridsmentioning

confidence: 85%

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

Bozorov

Zhao

Aisa

2019

Bioorganic & Medicinal Chemistry

579

289

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“…Notably, the diazo transfer is the preferred reaction pathway in the case of tosylazide [29], which possesses an electron-withdrawing substituent next to the azide group. At the same time, the more electron-rich phenylazide undergoes cycloaddition with 1,3-dicarbonyl compounds under the same conditions [31,32]. Asnitro-substituted benzofuroxans are known for their superelectrophilic nature [7,21,[33][34][35][36], we attribute the difference between azidonitrobenzofuroxan 2 and azidofuroxan derivatives [27] to the strong electron-withdrawing effect of the former.…”

Section: Resultsmentioning

confidence: 91%

The Reactivity of Azidonitrobenzofuroxans towards 1,3-Dicarbonyl Compounds: Unexpected Formation of Amino Derivative via the Regitz Diazo Transfer and Tautomerism Study

Chugunova

Газизов

Islamov

et al. 2021

IJMS

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Herein, we report on the reaction of nitro-substituted azidobenzofuroxans with 1,3-dicarbonyl compounds in basic media. The known reactions of benzofuroxans and azidofuroxans with 1,3-dicarbonyl compounds in the presence of bases are the 1,3-dipolar cycloaddition and the Beirut reaction. In contrast with this, azidonitrobenzofuroxan reacts with 1,3-carbonyl compounds through Regitz diazo transfer, which is the first example of this type of reaction for furoxan derivatives. This difference is seemingly due to the strong electron-withdrawing effect of the superelectrophilic azidonitrobenzofuroxan, which serves as the azido transfer agent rather than 1,3-dipole in this case.

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“…Finally, the key intermediates 12a-12e were produced by the reduction of 11a-11e with hydrazine hydrate as reducing agent. Other intermediates 13a-13i, which have been reported in our previous research [15], were combined with intermediates 12a-12e by a nucleophilic substitute reaction to get the target compounds B1-B27.…”

Section: Chemistrymentioning

confidence: 99%

“…After completion of the reaction, the solution was filtered, concentrated, and recrystallized to give a green solid. The preparation of intermediates 13a-13i was carried out according to our previous research [15].…”

Section: Preparation Of 4-(4-aminophenoxy)picolinamide or 4-(2-fluoromentioning

confidence: 99%

Design, Synthesis, and Biological Evaluation of Pyridineamide Derivatives Containing a 1,2,3-Triazole Fragment as Type II c-Met Inhibitors

et al. 2019

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A series of 4-(pyridin-4-yloxy)benzamide derivatives containing a 1,2,3-triazole fragment were designed, synthesized, and their inhibitory activity against A549, HeLa, and MCF-7 cancer cell lines was evaluated. Most compounds exhibited moderate to potent antitumor activity against the three cell lines. Among them, the promising compound B26 showed stronger inhibitory activity than Golvatinib, with IC50 values of 3.22, 4.33, and 5.82 μM against A549, HeLa, and MCF-7 cell lines, respectively. The structure–activity relationships (SARs) demonstrated that the modification of the terminal benzene ring with a single electron-withdrawing substituent (fluorine atom) and the introduction of a pyridine amide chain with a strong hydrophilic group (morpholine) to the hinge region greatly improved the antitumor activity. Meanwhile, the optimal compound B26 showed potent biological activity in some pharmacological experiments in vitro, such as cell morphology study, dose-dependent test, kinase activity assay, and cell cycle experiment. Finally, the molecular docking simulation was performed to further explore the binding mode of compound B26 with c-Met.

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Discovery of thinopyrimidine-triazole conjugates as c-Met targeting and apoptosis inducing agents

Cited by 31 publications

References 16 publications

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

1,2,3-Triazole-containing hybrids as leads in medicinal chemistry: A recent overview

The Reactivity of Azidonitrobenzofuroxans towards 1,3-Dicarbonyl Compounds: Unexpected Formation of Amino Derivative via the Regitz Diazo Transfer and Tautomerism Study

Design, Synthesis, and Biological Evaluation of Pyridineamide Derivatives Containing a 1,2,3-Triazole Fragment as Type II c-Met Inhibitors

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