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Synthesis and Antimicrobial Activity of 6-Thioxo-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]-quinazolin-2-one Derivatives.

Nosulenko IS, Voskoboynik OY, Berest GG, Safronyuk SL, Kovalenko SI, Kamyshnyi OM, Polishchuk NM, Sinyak RS, Katsev AV - Sci Pharm (2014)

Bottom Line: It was found that the nature of the substituents in positions 3, 4, and 5 of the corresponding 6-R-3-(3-R(1)-4-R(2)-5-R(3)-aminophenyl)-1,2,4-triazin-5-ones were affected on the terms of the reaction.The structures of compounds were proven by a complex of physicochemical methods ((1)H, (13)C NMR, LC-MS, and EI-MS).The results of the antibacterial and antifungal activity assay allowed the determination of the high sensitivity of Staphylococcus aureus ATCC 25923 (MIC 6.25-100 μg/mL, MBC 12.5-200 μg/mL) to the synthesized compounds.

View Article: PubMed Central - PubMed

Affiliation: Department of Organic and Bioorganic Chemistry, Zaporizhzhia State Medical University, Mayakovsky ave., 26, 69035, Zaporizhzhia, Ukraine.

ABSTRACT
Potassium 8-R(1)-9-R(2)-10-R(3)-3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-thiolates 2.1-2.26 were synthesized via cyclocondensation of 6-R-3-(3-R(1)-4-R(2)-5-R(3)-aminophenyl)-1,2,4-triazin-5-ones 1.1-1.26 with carbon disulfide, potassium hydroxide, and ethanol or with potassium O-ethyl dithiocarbonate in 2-propanol. The corresponding thiones 3.1-3.26 were obtained by treatment of 2.1-2.26 with hydrochloric acid. It was found that the nature of the substituents in positions 3, 4, and 5 of the corresponding 6-R-3-(3-R(1)-4-R(2)-5-R(3)-aminophenyl)-1,2,4-triazin-5-ones were affected on the terms of the reaction. The structures of compounds were proven by a complex of physicochemical methods ((1)H, (13)C NMR, LC-MS, and EI-MS). The results of the antibacterial and antifungal activity assay allowed the determination of the high sensitivity of Staphylococcus aureus ATCC 25923 (MIC 6.25-100 μg/mL, MBC 12.5-200 μg/mL) to the synthesized compounds.

No MeSH data available.


Related in: MedlinePlus

Synthesis of the potassium 3-R-8-R1-9-R2-10-R3-2-oxo-2H-[1, 2, 4]triazino[2, 3-c]-quinazoline-6-thiolates 2.1–2.26 and 3-R-8-R1-9-R2-10-R3-6-thioxo-6,7-dihydro-2H-[1, 2, 4]triazino[2, 3-c]quinazolin-2-ones 3.1–3.26
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Figure 1: Synthesis of the potassium 3-R-8-R1-9-R2-10-R3-2-oxo-2H-[1, 2, 4]triazino[2, 3-c]-quinazoline-6-thiolates 2.1–2.26 and 3-R-8-R1-9-R2-10-R3-6-thioxo-6,7-dihydro-2H-[1, 2, 4]triazino[2, 3-c]quinazolin-2-ones 3.1–3.26

Mentions: As starting compounds we used 6-R-3-(3-R1-4-R2-5-R3-2-aminophenyl)-1,2,4-triazin-5-ones (1.1–1.26), which were obtained according to known protocols, namely by nucleophilic cleavage of the pyrimidine fragment in 3-R-8-R1-9-R2-10-R3-2H-[1, 2, 4]triazino[2, 3-c]quinazolin-2-ones or hydrazinolysis of 2-aryl-[(3H-quinazolin-4-ylidene)hydrazono]acetic acids esters [14]. Synthesis of potassium thiolates 2.1–2.26 was performed by the interaction of initial compounds 1.1–1.26 with sulfur disulfide, ethanol, and potassium hydroxide in ethanol (Method A) or potassium O-ethyl dithiocarbonate in 2-propanol [8] 1.1–1.26 (Method B, Scheme 1). The products of the mentioned cyclocondensation were the individual compounds 2.1–2.26 with yields of 64-99%. Method B had some advantages: ease of execution, health safety, high yields, and purity of the final products. To prove the structure, the synthesized thiolates 2.1–2.26 were transformed in the corresponding thions 3.1–3.26 by acidifying the water solutions of the mentioned potassium salts with hydrochloric acid to pH 2–3. We noted that the substituents in positions 3, 4, and 5 in the corresponding 6-R-3-(2-aminophenyl)-1,2,4-triazino-5-ones (1.1–1.26) significantly affected the reaction process. So, according to LC-MS (APCI), the initial compounds, which contained the substituents chlorine, bromine, or iodine that were needed, increased the duration of heating to 8–10 hours.


Synthesis and Antimicrobial Activity of 6-Thioxo-6,7-dihydro-2H-[1,2,4]triazino[2,3-c]-quinazolin-2-one Derivatives.

Nosulenko IS, Voskoboynik OY, Berest GG, Safronyuk SL, Kovalenko SI, Kamyshnyi OM, Polishchuk NM, Sinyak RS, Katsev AV - Sci Pharm (2014)

Synthesis of the potassium 3-R-8-R1-9-R2-10-R3-2-oxo-2H-[1, 2, 4]triazino[2, 3-c]-quinazoline-6-thiolates 2.1–2.26 and 3-R-8-R1-9-R2-10-R3-6-thioxo-6,7-dihydro-2H-[1, 2, 4]triazino[2, 3-c]quinazolin-2-ones 3.1–3.26
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4318151&req=5

Figure 1: Synthesis of the potassium 3-R-8-R1-9-R2-10-R3-2-oxo-2H-[1, 2, 4]triazino[2, 3-c]-quinazoline-6-thiolates 2.1–2.26 and 3-R-8-R1-9-R2-10-R3-6-thioxo-6,7-dihydro-2H-[1, 2, 4]triazino[2, 3-c]quinazolin-2-ones 3.1–3.26
Mentions: As starting compounds we used 6-R-3-(3-R1-4-R2-5-R3-2-aminophenyl)-1,2,4-triazin-5-ones (1.1–1.26), which were obtained according to known protocols, namely by nucleophilic cleavage of the pyrimidine fragment in 3-R-8-R1-9-R2-10-R3-2H-[1, 2, 4]triazino[2, 3-c]quinazolin-2-ones or hydrazinolysis of 2-aryl-[(3H-quinazolin-4-ylidene)hydrazono]acetic acids esters [14]. Synthesis of potassium thiolates 2.1–2.26 was performed by the interaction of initial compounds 1.1–1.26 with sulfur disulfide, ethanol, and potassium hydroxide in ethanol (Method A) or potassium O-ethyl dithiocarbonate in 2-propanol [8] 1.1–1.26 (Method B, Scheme 1). The products of the mentioned cyclocondensation were the individual compounds 2.1–2.26 with yields of 64-99%. Method B had some advantages: ease of execution, health safety, high yields, and purity of the final products. To prove the structure, the synthesized thiolates 2.1–2.26 were transformed in the corresponding thions 3.1–3.26 by acidifying the water solutions of the mentioned potassium salts with hydrochloric acid to pH 2–3. We noted that the substituents in positions 3, 4, and 5 in the corresponding 6-R-3-(2-aminophenyl)-1,2,4-triazino-5-ones (1.1–1.26) significantly affected the reaction process. So, according to LC-MS (APCI), the initial compounds, which contained the substituents chlorine, bromine, or iodine that were needed, increased the duration of heating to 8–10 hours.

Bottom Line: It was found that the nature of the substituents in positions 3, 4, and 5 of the corresponding 6-R-3-(3-R(1)-4-R(2)-5-R(3)-aminophenyl)-1,2,4-triazin-5-ones were affected on the terms of the reaction.The structures of compounds were proven by a complex of physicochemical methods ((1)H, (13)C NMR, LC-MS, and EI-MS).The results of the antibacterial and antifungal activity assay allowed the determination of the high sensitivity of Staphylococcus aureus ATCC 25923 (MIC 6.25-100 μg/mL, MBC 12.5-200 μg/mL) to the synthesized compounds.

View Article: PubMed Central - PubMed

Affiliation: Department of Organic and Bioorganic Chemistry, Zaporizhzhia State Medical University, Mayakovsky ave., 26, 69035, Zaporizhzhia, Ukraine.

ABSTRACT
Potassium 8-R(1)-9-R(2)-10-R(3)-3-R-2-oxo-2H-[1,2,4]triazino[2,3-c]quinazoline-6-thiolates 2.1-2.26 were synthesized via cyclocondensation of 6-R-3-(3-R(1)-4-R(2)-5-R(3)-aminophenyl)-1,2,4-triazin-5-ones 1.1-1.26 with carbon disulfide, potassium hydroxide, and ethanol or with potassium O-ethyl dithiocarbonate in 2-propanol. The corresponding thiones 3.1-3.26 were obtained by treatment of 2.1-2.26 with hydrochloric acid. It was found that the nature of the substituents in positions 3, 4, and 5 of the corresponding 6-R-3-(3-R(1)-4-R(2)-5-R(3)-aminophenyl)-1,2,4-triazin-5-ones were affected on the terms of the reaction. The structures of compounds were proven by a complex of physicochemical methods ((1)H, (13)C NMR, LC-MS, and EI-MS). The results of the antibacterial and antifungal activity assay allowed the determination of the high sensitivity of Staphylococcus aureus ATCC 25923 (MIC 6.25-100 μg/mL, MBC 12.5-200 μg/mL) to the synthesized compounds.

No MeSH data available.


Related in: MedlinePlus