Synthesis, antitumor evaluation and 3D-QSAR studies of [1,2,4]triazolo[4,3- b ][1,2,4,5]tetrazine derivatives

Yang, Zhen-Zhen; Ke, Zhong-Lu; Xi, Limin; Qing, Yan; Yang, Wu; Zhu, Lei; Lin, Fei-lei; Lv, Wei-ke; Wu, Heng; Wang, John; Li, Haibo

doi:10.1016/j.bmcl.2016.08.078

Cited by 17 publications

(6 citation statements)

References 29 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…There are few reported examples of tetrazine motifs in biologically active molecules, and structure–activity relationship (SAR) studies that include this unusual heterocycle have historically been limited largely due to an inability to rapidly and consistently generate unsymmetrical substituted s -tetrazines. We therefore became interested in utilizing our optimized Suzuki conditions to generate a direct s -tetrazine analog of an existing molecule ( 12 ) and were aware of a report describing 3,6-substituted pyridazines as acetylcholinesterase (AChE) inhibitors, structurally related to minaprine (Scheme ).…”

mentioning

confidence: 99%

Preparation of Unsymmetrical 1,2,4,5-Tetrazines via a Mild Suzuki Cross-Coupling Reaction

et al. 2017

View full text Add to dashboard Cite

N-Alkyl substituted chlorotetrazines were coupled with various boronic acids under Suzuki conditions in high yield at room temperature, giving a mild and straightforward synthetic route toward diverse unsymmetrical 1,2,4,5-tetrazines, a rare heteroarene. This chemistry not only expands the known substrate scope of tetrazine cross-coupling reactions but also allows for the synthesis of novel, tetrazine-containing biologically active molecules with improved DMPK properties.

show abstract

mentioning

confidence: 99%

Preparation of Unsymmetrical 1,2,4,5-Tetrazines via a Mild Suzuki Cross-Coupling Reaction

et al. 2017

View full text Add to dashboard Cite

show abstract

“…12,13 Next, compound 1 was reacted with 80% hydrazine hydrate at 0–20 °C for 0.5 h in acetonitrile as the solvent to give compound 2 . 8,14–16 Subsequent cyclization of 2 with a stoichiometric amount of triethyl orthoformate and a catalytic amount of p -toluenesulfonic acid in ethanol yielded compound 3 . 17 Finally, the title compounds 4a-f were obtained from compound 3 by treatment with the corresponding alkyl diamine in dioxane or ethyl acetate.…”

Section: Resultsmentioning

confidence: 99%

“…TZXU 1–2 : 1.26-2.24 μM, 1.09-1.90 μM, and 1.16-1.61 μM, respectively). 8,9 In addition, N '-(4-((4-([1,2,4]triazolo [4,3- b ][1,2,4,5]tetrazin-6-yl)piperazin-1-yl)methyl)benzoyl)-2-substituted benzohydrazide derivatives show strong anticancer activities against A549, Bewo and HepG2 cell lines (e.g. TZXU-3: 8.4 μM, 5.2 μM and 2.4 μM, respectively).…”

Section: Introductionmentioning

confidence: 99%

Synthesis, biological evaluation and molecular docking of N, N’-bis([1,2,4]triazole[4,3-b][1,2,4,5]tetrazine-6-yl)alkylamine derivatives as potent c-Met antagonists

Pei

Yang

et al. 2022

Journal of Chemical Research

View full text Add to dashboard Cite

A series of N, N’-bis([1,2,4]triazole[4,3- b][1,2,4,5]tetrazine-6-yl)alkylamine derivatives is designed, synthesized and evaluated for their inhibition activities against three tumor cell lines and c-Met kinase activity in vitro. These compounds are fully characterized by 1H NMR, 13C NMR, MS, IR and elemental analysis. Antitumor experiments indicate that some of these compounds exhibit significant inhibition activities against A549, Bewo and MCF-7 cancer cell lines. Among them, the IC50 values of 4a indicate better antitumor activities against the A549 (1.21 μM), Bewo (0.68 μM) and MCF-7 (3.74 μM) cell lines than the positive agent cisplatin (9.97 μM for A549, 10.46 μM for Bewo, and 15.03 μM for MCF-7), respectively.

show abstract

“…Xu et al. carried out three dimensional quantitative structure-activity relationship (3D-QSAR) on [ 1 , 2 , 4 ]triazolo[4,3- b ][1,2,4,5]tetrazine derivatives with antitumor activities against MCF-7 cell [ 109 ]. The results of CoMFA (q 2 : 0.716, r 2 : 0.985) and CoMSIA (q 2 : 0.723, r 2 : 0.976) generated models with good predictive abilities.…”

Section: Biological Activities Of 124-triazole Derivativesmentioning

confidence: 99%

An insight on medicinal attributes of 1,2,4-triazoles

Aggarwal

Sumran²

2020

European Journal of Medicinal Chemistry

216

View full text Add to dashboard Cite

The present review aims to summarize the pharmacological profile of 1,2,4-triazole, one of the emerging privileged scaffold, as antifungal, antibacterial, anticancer, anticonvulsant, antituberculosis, antiviral, antiparasitic, analgesic and anti-inflammatory agents, etc. along with structure-activity relationship. The comprehensive compilation of work carried out in the last decade on 1,2,4-triazole nucleus will provide inevitable scope for researchers for the advancement of novel potential drug candidates having better efficacy and selectivity.

show abstract

Synthesis, antitumor evaluation and 3D-QSAR studies of [1,2,4]triazolo[4,3- b ][1,2,4,5]tetrazine derivatives

Cited by 17 publications

References 29 publications

Preparation of Unsymmetrical 1,2,4,5-Tetrazines via a Mild Suzuki Cross-Coupling Reaction

Preparation of Unsymmetrical 1,2,4,5-Tetrazines via a Mild Suzuki Cross-Coupling Reaction

Synthesis, biological evaluation and molecular docking of N, N’-bis([1,2,4]triazole[4,3-b][1,2,4,5]tetrazine-6-yl)alkylamine derivatives as potent c-Met antagonists

An insight on medicinal attributes of 1,2,4-triazoles

Contact Info

Product

Resources

About