Tandem heterocyclization of 2‐(azolyl‐(azinyl‐))anilines as an efficient method for preparation of substituted pyrrolo[1,2‐<i>a</i>]azolo‐(azino‐)[<i>c</i>]quinazolines

Stavytskyi, Viktor; Voskoboynik, О. Yu.; Antypenko, O. M.; Красовська, Н. І.; Shabelnyk, Konstantyn; Konovalova, Irina S.; Shishkyna, Svitlana; Kholodniak, Sergiy; Коваленко, Сергій Іванович

doi:10.1002/jhet.3862

Cited by 3 publications

(2 citation statements)

References 16 publications

(36 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Recently, the pyrrolo[1,2-а][1,2,4]triazino[2,3-с]quinazoline heterocyclic system was described as a promising "scaffold" for construction of novel bioactive compounds [8]. Additionally, the concept of the purposeful structural optimization of the abovementioned heterocyclic system previously developed [9] allowed us to synthesize the novel 3-…”

Section: эфиры и амиды 3-r-28-диоксо-78-дигидро-2н-пирроло[12-а]-[mentioning

confidence: 99%

See 1 more Smart Citation

Esters and amides of 3-R-2,8-dioxo-7,8-dihydro2H-pyrrolo[1,2-a][1,2,4]triazino[2,3-c]quinazolin-5a(6H)-carboxylic(-propanoic) acids: synthesis and biological activity

Stavytskyi

Носуленко

Kandybey

et al. 2020

J. org. pharm. chem.

View full text Add to dashboard Cite

It is known that carboxyl groups bonded to aryl or hetaryl moieties play a role of the "pharmacophore" fragment in most NSAID molecules. It should be mentioned that the carboxyl group may cause the appearance of toxic effects and is characterized by unsatisfactory pharmacokinetic properties. The structural modification of the carboxyl group, including its bioisosteric replacement, is among the most widely used approaches in medicinal chemistry to improve pharmacodynamic, pharmacokinetic and technological characteristics. Aim. To develop the synthetic procedures for functional derivatives of 3-R-2,8-dioxo-7,8-dihydro-2Н-pyrrolo[1,2-а]-[1,2,4]triazino[2,3-с]quinazoline-5а(6Н)-carboxylic(-propanoic) acids, study the effect of the carboxyl group chemical modification on the LOX-inhibiting and antiradical activity as a possible mechanism of the pharmacological activity. Results and discussion. The synthesis of esters of 3-(2,8-dioxo-3-R 1-7,8-dihydro-2H-pyrrolo[1,2-a][1,2,4]triazino[2,3-c]quinazolin-5a(6H)-yl)carboxylic(propanoic) acids was conducted by esterification of the corresponding acids and tandem heterocyclization of 2-(6-R 1-2,5-dihydro-5-оxo-1,2,4-triazino-3-yl)anilines with diethyl 4-oxoheptanedioate. The synthesis of amides was conducted by aminolysis of N-acylimidazolides generated in situ. The antiradical and LOX-inhibiting activities of the compounds obtained were studied as possible mechanisms of the anti-inflammatory activity. The series of the compounds revealed the LOX-inhibiting activity that was comparable with the effect of the reference compound-nordihydroguaiaretic acid. Experimental part. The synthetic procedures were conducted according to the commonly used methods. The purity and the structure of the compounds obtained were proven by modern physicochemical methods (1 H and 13 C NMR-spectroscopy, LC-MS-spectrometry). The antiradical activity was measured by the ability to scavenge a DPPH-radical. The study of the LOX-inhibiting activity was performed using soybean LOX as an enzyme and linolenic acid as a substrate. Conclusions. The methods for the synthesis of esters and amides of 2,8-dioxo-3-R 1-7,8-dihydro-2Hpyrrolo[1,2-a][1,2,4]triazino[2,3-c]quinazolin-5a(6H)-carboxilic(propanoic) acids have been developed. The abovementioned transformations were conducted by alcoholysis of generated in situ acyl halides and aminolysis of N-acylimidazolides, respectively. The more efficient approach for the synthesis of the target esters via condensation of 2-(6-R 1-2,5-dihydro-5-oxo-1,2,4-triazino-3-yl)anilines with diethyl 4-oxoheptanedioate has been proposed. It has been found that the highest radical scavenging and LOX-inhibiting activities are characteristic for hetarylpropanoic acids that contain electron withdrawing substituents in position 3, as well as fluorine atoms in positions 11 and 12. The chemical modification of the carboxylic group in most cases results in a decrease or the loss of the activity.

show abstract

Section: эфиры и амиды 3-r-28-диоксо-78-дигидро-2н-пирроло[12-а]-[mentioning

confidence: 99%

“…The synthetic studies were conducted according to the general approach to the search of potential biologically active substances using reagents of companies Sigma-Aldrich (Missouri, USA) and Enamine (Kyiv, Ukraine). [8,15]. 3-(3-R 1 -2,8-dioxo-7,8-dihydro-2H-pyrrolo[1,2-a]-[1,2,4…”

Section: Experimental Partmentioning

confidence: 99%

Esters and amides of 3-R-2,8-dioxo-7,8-dihydro2H-pyrrolo[1,2-a][1,2,4]triazino[2,3-c]quinazolin-5a(6H)-carboxylic(-propanoic) acids: synthesis and biological activity

Stavytskyi

Носуленко

Kandybey

et al. 2020

J. org. pharm. chem.

View full text Add to dashboard Cite

show abstract

Synthesis of isoxazolylpyrrolones by three-component reaction of α-ketoglutaric acid or its diethyl ester with 3-amino-5-methylisoxazole and aromatic aldehydes

Sakhno

Radchenko

Muravyova

et al. 2021

Chem Heterocycl Comp

View full text Add to dashboard Cite

5+1-Heterocyclization as preparative approach for carboxy-containing triazolo[1,5-c]quinazolines with anti-inflammatory activity

Krasovska,

Berest,

Belenichev

et al. 2024

European Journal of Medicinal Chemistry

View full text Add to dashboard Cite

Tandem heterocyclization of 2‐(azolyl‐(azinyl‐))anilines as an efficient method for preparation of substituted pyrrolo[1,2‐a]azolo‐(azino‐)[c]quinazolines

Cited by 3 publications

References 16 publications

Esters and amides of 3-R-2,8-dioxo-7,8-dihydro2H-pyrrolo[1,2-a][1,2,4]triazino[2,3-c]quinazolin-5a(6H)-carboxylic(-propanoic) acids: synthesis and biological activity

Esters and amides of 3-R-2,8-dioxo-7,8-dihydro2H-pyrrolo[1,2-a][1,2,4]triazino[2,3-c]quinazolin-5a(6H)-carboxylic(-propanoic) acids: synthesis and biological activity

Synthesis of isoxazolylpyrrolones by three-component reaction of α-ketoglutaric acid or its diethyl ester with 3-amino-5-methylisoxazole and aromatic aldehydes

5+1-Heterocyclization as preparative approach for carboxy-containing triazolo[1,5-c]quinazolines with anti-inflammatory activity

Contact Info

Product

Resources

About

Tandem heterocyclization of 2‐(azolyl‐(azinyl‐))anilines as an efficient method for preparation of substituted pyrrolo[1,2‐a]azolo‐(azino‐)[c]quinazolines

Cited by 3 publications

References 16 publications

Esters and amides of 3-R-2,8-dioxo-7,8-dihydro2H-pyrrolo[1,2-a][1,2,4]­triazino[2,3-c]quinazolin-5a(6H)-carboxylic(-propanoic) acids: synthesis and biological activity

Esters and amides of 3-R-2,8-dioxo-7,8-dihydro2H-pyrrolo[1,2-a][1,2,4]­triazino[2,3-c]quinazolin-5a(6H)-carboxylic(-propanoic) acids: synthesis and biological activity

Synthesis of isoxazolylpyrrolones by three-component reaction of α-ketoglutaric acid or its diethyl ester with 3-amino-5-methylisoxazole and aromatic aldehydes

5+1-Heterocyclization as preparative approach for carboxy-containing triazolo[1,5-c]quinazolines with anti-inflammatory activity

Contact Info

Product

Resources

About

Esters and amides of 3-R-2,8-dioxo-7,8-dihydro2H-pyrrolo[1,2-a][1,2,4]triazino[2,3-c]quinazolin-5a(6H)-carboxylic(-propanoic) acids: synthesis and biological activity

Esters and amides of 3-R-2,8-dioxo-7,8-dihydro2H-pyrrolo[1,2-a][1,2,4]triazino[2,3-c]quinazolin-5a(6H)-carboxylic(-propanoic) acids: synthesis and biological activity