2-Heteroaryl-[1,2,4]triazolo[1,5-c]quinazoline-5(6 H)-thiones and Their S-Substituted Derivatives: Synthesis, Spectroscopic Data, and Biological Activity

In the continuing search for novel, biologically effective heterocyclic agents, several methods for the synthesis of 2‐heteroaryl‐[1,2,4]triazolo[1,5‐c]quinazoline‐5(6 H)‐thiones have been developed: thiolation of oxo derivatives, [5+1] cyclocondensation of [2‐(3‐heteroaryl‐[1,2,4]triazol‐5‐yl)pheny...

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Bibliographic Details
Published in:	ChemPlusChem (Weinheim, Germany) Vol. 80; no. 6; pp. 980 - 989
Main Authors:	Bilyi, Andrii K., Antypenko, Lyudmyla M., Ivchuk, Vitalii V., Kamyshnyi, Oleksandr M., Polishchuk, Natalya M., Kovalenko, Sergiy I.
Format:	Journal Article
Language:	English
Published:	Weinheim WILEY-VCH Verlag 01-06-2015 WILEY‐VCH Verlag
Subjects:	antibacterial agents antifungal agents antitumor agents biological activity heterocycles antifungal agents biological activity heterocycles antibacterial agents antitumor agents
Online Access:	Get full text
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Summary:	In the continuing search for novel, biologically effective heterocyclic agents, several methods for the synthesis of 2‐heteroaryl‐[1,2,4]triazolo[1,5‐c]quinazoline‐5(6 H)‐thiones have been developed: thiolation of oxo derivatives, [5+1] cyclocondensation of [2‐(3‐heteroaryl‐[1,2,4]triazol‐5‐yl)phenyl]amines with carbon disulfide, potassium ethyl xanthogenate, or aryl isothiocyanates, and in situ reaction of 2‐isothiocyanatobenzonitrile with hydrazides. A series of N‐R‐2‐[(2‐heteroaryl‐[1,2,4]triazole‐[1,5‐c]quinazoline‐5‐yl)thio]acetamides were obtained by aminolysis of the corresponding acetic acids and alkylation of potassium thiolates with N‐R‐2‐chloroacetamides. It was established that some potassium thiolates, 4 a–4 d, 4 h, and 4 i, had high antibacterial activity against Staphylococcus aureus with a minimum inhibitory concentration of 12.5 μg mL−1 and minimum bactericidal concentration of 25 μg mL−1, which exceeded the values for trimethoprim. In addition, {2‐[3‐(1 H‐indole‐2‐yl)‐1 H‐1,2,4‐triazol‐5‐yl]phenyl}amine 2 i was investigated in the concentration range 100–0.01 μM at 59 lines of nine cancer cell types, and showed a mean effective concentration at 3.12–7.03 μM and cytotoxic effect at 15.56–67.38 μM. The possible mechanisms of activity were predicted by molecular docking studies to S. aureus dihydrofolate reductase and epidermal growth factor receptor kinase. Killer instinct: In the search for effective biologically active heterocycles, it has been found that potassium 2‐heteroaryl‐[1,2,4]triazolo[1,5‐c]quinazoline‐5‐thiolates have high antibacterial activity against Staphylococcus aureus. In addition, {2‐[3‐(1 H‐indole‐2‐yl)‐1 H‐1,2,4‐triazol‐5‐yl]phenyl}amine has high anticancer activity in terms of 50 % and total growth inhibition (see figure).
Bibliography:	Enamine Ltd. ArticleID:CPLU201500051 ark:/67375/WNG-Q6MM3DK4-7 istex:12A6BA085CA1594EC182BD91A134B37D904BE2DD ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	2192-6506 2192-6506
DOI:	10.1002/cplu.201500051