Benzopyrroloxazines containing a bridgehead nitrogen atom as promising scaffolds for the achievement of biologically active agents

Grande, Fedora; Occhiuzzi, Maria Antonietta; Ioele, Giuseppina; Ragno, Gaetano; Garofalo, Antonio

doi:10.1016/j.ejmech.2018.03.061

Cited by 17 publications

(12 citation statements)

References 84 publications

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“…The low activation barrier of acetylene-allene isomerization of N-propargylpyrrol-2-ylmethanol indicates its complete transition to the experimentally observed N-allenylpyrrol-2-ylmethanol (9). The latter, in turn, is a precursor of the following products: the most thermodynamically stable N-allenyl-2-[(propargyloxy)methyl]-1H-pyrrole (15) and the target 3-Me-1H-pyrrolo[2,1-c] [1,4] oxazine (27). Compound 27 is formed as a result of the intramolecular cyclization of 9, upon the attack of an alcohol group at the allene internal atom, while product 15 is produced through the S N 2 reaction of 9 with the second molecule of propargyl chloride.…”

Section: Resultsmentioning

confidence: 94%

“…General procedure for synthesis of (1-(propa-1,2-dien-1-yl) of 2-((prop-2-yn-1-yloxy)methyl)-1-(propa-1,2-dien-1-yl)-1H-pyrrole (15). A mixture of the pyrrole (1.2 mmol), KOH pellets (15 % water content, 0.31 g, 4.8 mmol) and DMSO (water content < 0.2 %) (2 mL) was stirred at r.t. for 45 min.…”

Section: Methodsmentioning

confidence: 99%

“…Thus, the most probable resulting disubstituted adducts is N-allenyl-2-[(propargyloxy)methyl]-1H-pyrrole (15). The addition of alcoholate ion at the propargyl terminal atom of 6 through the transition state TS 6!20 (Figure 11a) with trans-distortion of the acetylene fragment occurs with an activation barrier of ΔG � = 17.2 kcal/mol and leads to the seven-membered oxazepine cycle (20) with the enthalpy increasing by ΔH = + 9.7 kcal/mol (Scheme 5).…”

Section: Formation Of Disubstituted Adducts Of 1h-pyrrol-2-ylmethanolmentioning

confidence: 99%

“…[14] The synthesis of 1,4-oxazines annelated with the pyrrole and more often indole skeleton is of considerable interest. Such structural fragments are excellent intermediates in the chemistry of bioactive compounds: [15] they exhibit anti-inflammatory, anti-viral, anti-tumor, anti-bacterial, anti-fungal, antimalarial, anti-HIV and anxiolytic activity, and also stimulate the central nervous system. For instance, a novel GSK588045 [16] possesses antagonist activity at 5-HT1 A/1B/1D receptors and nanomolar affinity for the serotonin transporter, which was in development for the treatment of depression and anxiety.…”

Section: Introductionmentioning

confidence: 99%

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Base‐Promoted Formation of an Annelated Pyrrolo‐1,4‐oxazine Ensemble from 1H‐pyrrol‐2‐ylmethanol and Propargyl Chloride: A Theoretical and Experimental Study

et al. 2019

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Base-Promoted Formationofa nA nnelated Pyrrolo-1,4-oxazine Ensemblefrom 1H-pyrrol-2-ylmethanol and Propargyl Chloride:ATheoretical and Experimental Study What prompted you to investigate this topic/problem?The Irkutsk School of Organic Chemistry has rich and broad experience in building and functionalizing pyrrole systems in ac onvenient and universal fashion. The work presented is ac ontinuation of as eries of investigations to activate several reactive centers of pyrrole with the aim to synthesize previously unknown compounds with promising properties, such as drugs and precursors of materials with specific characteristics.Invited for this month'sc over is the group of Prof. Dr.N adezhda M. Vitkovskaya at Irkutsk State University and the group of Dr.A ndrey V. Ivanova tt he A. E. Favorsky Irkutsk Institute of Chemistry,R ussian Federation.The image shows that three different pyrrole derivatives can be obtained from the same starting reagents. The reaction is easily controlled by the ratio of the reagents, the amount of alkali, and the degree of dilution.T he three strings of the balalaika (a Russianf olk instrument) that represent these parametersc an produce melodies from the same notes symbolizing the reagents. The sheets with quantum-chemical calculations under the musical notebooks ymbolize thatt he experimental work is based on the theoretical investigations. Read the full text of the article at

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Section: Resultsmentioning

confidence: 94%

Section: Methodsmentioning

confidence: 99%

Section: Formation Of Disubstituted Adducts Of 1h-pyrrol-2-ylmethanolmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Base‐Promoted Formation of an Annelated Pyrrolo‐1,4‐oxazine Ensemble from 1H‐pyrrol‐2‐ylmethanol and Propargyl Chloride: A Theoretical and Experimental Study

et al. 2019

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“…Therefore, it is important to study newer drugs with reduced resistance [21] . Several pyrrole fused benzoxazines are known to exhibit antibacterial activity [5c,7b,22] . Here, the pyrrole‐fused benzoxazinones/quinoxalinones depicted in table 1 were explored for antibacterial activity.…”

Section: Resultsmentioning

confidence: 99%

Pyrrole‐Fused Benzoxazinones/Quinoxalinones: Molecular Dynamic Simulation, Antiproliferative and Antibacterial Activities

et al. 2021

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A series of novel pyrrole fused benzoxazinones/quinoxalinones has been evaluated for antiproliferative activity against breast cancer cell line, MCF7 and treatment-resistant triple-negative breast cancer cell line MDA-MB-231. Among which pyrroloquinoxalinones exhibited higher cytotoxicity. Furthermore, they showed insignificant cellular cytotoxicity in normal human cell HEK293T when treated with their respective IC 50 concentrations. In silico molecular docking, study suggests that the inhibitory mechanism of pyrroloquinoxalinones probably mediated via modulation of breast cancer targets such as VEGFR2 and EGFR. The stability of target protein (VEGFR2 and EGFR)ligand (pyrroloquinoxalinones) interactions was validated by Molecular dynamic simulation (50 ns). Additionally, pyrrolobenzoxazinones/quinoxalinones were evaluated for in vitro antibacterial activity against Gram-positive and Gram-negative bacterial strains. All the compounds exhibited significant antibacterial activity (IC 50 0.034-15.4 μM) towards the tested bacterial strains. These findings indicate that pyrrolobenzoxazinones/quinoxalinones are valuable scaffolds for the development of potent anticancer and antibacterial compounds.

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A Short‐Cut to Substituted Fused Pyrrolo[2,1‐c][1,4]oxazines: A Hybrid Theoretical and Experimental Study

et al. 2023

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The effect of substituents in the pyrrole ring and at the triple bond on the formation of fused pyrrolooxazines from 1H‐pyrrol‐2‐ylmethanols and propargyl chlorides has been theoretically and experimentally studied. The energy characteristics of the reaction are evaluated using quantum‐chemical calculations (CBS‐Q//B3). A one‐pot transition metal‐free synthesis of substituted 3‐methyl‐1H‐pyrrolo[2,1‐c][1,4]oxazines in good yields has been implemented in the superbasic system NaOH/DMSO.

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Benzopyrroloxazines containing a bridgehead nitrogen atom as promising scaffolds for the achievement of biologically active agents

Cited by 17 publications

References 84 publications

Base‐Promoted Formation of an Annelated Pyrrolo‐1,4‐oxazine Ensemble from 1H‐pyrrol‐2‐ylmethanol and Propargyl Chloride: A Theoretical and Experimental Study

Base‐Promoted Formation of an Annelated Pyrrolo‐1,4‐oxazine Ensemble from 1H‐pyrrol‐2‐ylmethanol and Propargyl Chloride: A Theoretical and Experimental Study

Pyrrole‐Fused Benzoxazinones/Quinoxalinones: Molecular Dynamic Simulation, Antiproliferative and Antibacterial Activities

A Short‐Cut to Substituted Fused Pyrrolo[2,1‐c][1,4]oxazines: A Hybrid Theoretical and Experimental Study

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