Formation, structure and heterocyclization of aminoguanidine and ethyl acetoacetate condensation products

Erkin, A. V.; Krutikov, V. I.

doi:10.1134/s1070363209060309

Cited by 9 publications

(10 citation statements)

References 8 publications

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“…Compounds 2a – d were easily chlorinated with phosphorus oxychloride under reflux for 6 h, affording the respective 7-chloro[1,2,4]triazolo[1,5- a ]pyrimidines 3a – d in 58–90% yields. Compounds 3a and 3b showed identical spectroscopic data to those reported in the literature [ 23 , 25 , 26 , 27 , 28 , 29 , 30 , 31 ]. Spectroscopic data of compounds 3c and 3d were in agreement with the proposed structures.…”

Section: Resultssupporting

confidence: 73%

“…The synthetic route to [1,2,4]triazolo[1,5- a ]pyrimidine derivatives 4 – 29 is shown in Figure 3 . Condensation of 3-amino-1,2,4-triazoles 1a – c with ethyl acetoacetate or ethyl 4,4,4-trifluoroacetoacetate in refluxing toluene, in the presence of catalytic p -toluenesulfonic acid, gave [1,2,4]triazolo[1,5- a ]pyrimidin-7(4 H )-ones 2a – d in 50–90% yields after 24 h, as previously described in the literature [ 23 , 24 , 30 , 31 ]. Spectroscopic data of compounds 2a – d were in agreement with the literature, and X-ray crystallography showed 2c as their keto-tautomers [ 24 ].…”

Section: Resultssupporting

confidence: 63%

“…The [1,2,4]triazolo[1,5- a ]pyrimidin-7(4 H )-ones 2a , b were prepared according to methodology described in the literature [ 23 , 24 , 30 , 31 ]. A mixture of a 3-amino-1,2,4-triazole derivative ( 1c ) (20 mmol) and ethyl acetoacetate or ethyl 4,4,4-trifluoroacetoacetate (15 mL) was stirred at room temperature for 30 minutes.…”

Section: Methodsmentioning

confidence: 99%

“…The 7-chloro[1,2,4]triazolo[1,5- a ]pyrimidine 3a , b were prepared according to methodology described in the literature [ 23 , 30 , 31 ]. To a [1,2,4]triazolo[1,5- a ]pyrimidin-7(4 H )-one derivative 2c , d (4.5 mmol) was added phosphorus oxychloride (10 mL).…”

Section: Methodsmentioning

confidence: 99%

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New Trifluoromethyl Triazolopyrimidines as Anti-Plasmodium falciparum Agents

et al. 2012

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According to the World Health Organization, half of the World’s population, approximately 3.3 billion people, is at risk for developing malaria. Nearly 700,000 deaths each year are associated with the disease. Control of the disease in humans still relies on chemotherapy. Drug resistance is a limiting factor, and the search for new drugs is important. We have designed and synthesized new 2-(trifluoromethyl)[1,2,4]triazolo[1,5-a]pyrimidine derivatives based on bioisosteric replacement of functional groups on the anti-malarial compounds mefloquine and amodiaquine. This approach enabled us to investigate the impact of: (i) ring bioisosteric replacement; (ii) a CF3 group substituted at the 2-position of the [1,2,4]triazolo[1,5-a]pyrimidine scaffold and (iii) a range of amines as substituents at the 7-position of the of heterocyclic ring; on in vitro activity against Plasmodium falciparum. According to docking simulations, the synthesized compounds are able to interact with P. falciparum dihydroorotate dehydrogenase (PfDHODH) through strong hydrogen bonds. The presence of a trifluoromethyl group at the 2-position of the [1,2,4]triazolo[1,5-a]pyrimidine ring led to increased drug activity. Thirteen compounds were found to be active, with IC50 values ranging from 0.023 to 20 µM in the anti-HRP2 and hypoxanthine assays. The selectivity index (SI) of the most active derivatives 5, 8, 11 and 16 was found to vary from 1,003 to 18,478.

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Section: Resultssupporting

confidence: 73%

Section: Resultssupporting

confidence: 63%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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New Trifluoromethyl Triazolopyrimidines as Anti-Plasmodium falciparum Agents

et al. 2012

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“…The pyrazole moiety was modified by replacing one of the methyl groups with a hydroxyl group. This was performed by using aminoguanidine as the precursor and reacting it with a β-keto ester 33 such as ethyl acetoacetate to give a pyrazolone derivative 28 (Scheme 4). The similar synthetic methodology gave the 4-methylpyrazolone derivative 29 .…”

Section: Resultsmentioning

confidence: 99%

Small Polar Hits against S. aureus: Screening, Initial Hit Optimization, and Metabolomic Studies

et al. 2019

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The global prevalence of antibacterial resistance requires new antibacterial drugs with novel chemical scaffolds and modes of action. It is also vital to design compounds with optimal physicochemical properties to permeate the bacterial cell envelope. We described an approach of combining and integrating whole cell screening and metabolomics into early antibacterial drug discovery using a library of small polar compounds. Whole cell screening of a diverse library of small polar compounds against Staphylococcus aureus gave compound 2. Hit expansion was carried out to determine structure–activity relationships. A selection of compounds from this series, together with other screened active compounds, was subjected to an initial metabolomics study to provide a metabolic fingerprint of the mode of action. It was found that compound 2 and its analogues have a different mode of action from some of the known antibacterial compounds tested. This early study highlighted the potential of whole cell screening and metabolomics in early antibacterial drug discovery. Future works will require improving potency and performing orthogonal studies to confirm the modes of action.

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