Synthesis and biological evaluation of novel fused triazolo[4,3-$a$] pyrimidinones

Abstract

The reaction of thione 3 or its 2-methylthio derivative 4 with hydrazonoyl halides 5a-l, in the presence of triethylamine, yielded the corresponding triazolo[4,3-a ]pyrimidin-5(1 H) -ones 8a-l. The structure of compounds 8a-l was further confirmed by the reaction of 3 with the appropriate active chloromethylenes 11a-c followed by coupling of the products with benzenediazonium chloride to afford the azo-coupling products 6b, f, and j, which were converted in situ to 8b, f, and j. 2-Hydrazinyl-pyrido[3',2':4,5]thieno[3,2-d ]pyrimidin-4(3 H) -one ( 13) was prepared and condensed with different aldehydes 14a-f to give the corresponding hydrazone derivatives 15a-f. Oxidative cyclization of the hydrazones 15a-f give the corresponding triazolo[4,3-a ] pyrimidin-5(1 H) -one derivatives 16a-f.The antimicrobial activity of the products was evaluated and the results revealed that compounds 8f and 15f showed strong activity against gram-positive bacteria while compound 15d showed the highest activity against gramnegative bacteria. Moreover, compounds 15b, 8d, 8e, 8c, 8l, and 8j exhibited significant antifungal activity. In addition, the antitumoral activity of the synthesized products against different cancer cell lines was determined and the results revealed that compound 12c was the most active against MCF-7, HepG-2, HCT-116, and HeLa with IC 50 values of 0.51, 0.72, 0.95, and 0.95, respectively, as compared with doxorubicin as positive control.

Efficient synthesis and molecular docking of novel antibacterial pyrimidines and their related fused heterocyclic derivatives

“…[42] S C H E M E 2 Synthesis of [1,2,4] Synthesis of a related fused [1,2,4]triazole nucleus was achieved via the reaction of 26 with the appropriate hydrazonyl chlorides 10. [24] Thus, compound 26 reacted with hydrazonyl chloride 10a in dioxane in the presence of an equivalent amount of triethylamine. The reaction mixture was heated at reflux till no methanethiol gases were evolved.…”

“…Pyrimidines and their related fused heterocyclic derivatives possess antibacterial, antifungal, antiviral, anti-influenza, antioxidant, anti-inflammatory, antimalarial, antiproliferative, and antitumor activities. [20][21][22][23][24] Our research group has published many researches in the field of synthesis of pyrimidine derivatives and their related fused heterocyclic derivatives, [25][26][27][28][29][30] because they possess broad spectrum of bioactivities. [17][18][19] Moreover, [1,2,4] triazolopyrimidine derivatives exhibit antimicrobial, antifungal, antioxidant, anti-inflammatory, antimalarial, analgesic, and antitumor activities.…”

“…triazolopyrimidine derivatives exhibit antimicrobial, antifungal, antioxidant, anti-inflammatory, antimalarial, analgesic, and antitumor activities. [20][21][22][23][24] Our research group has published many researches in the field of synthesis of pyrimidine derivatives and their related fused heterocyclic derivatives, [25][26][27][28][29][30] because they possess broad spectrum of bioactivities. [31][32][33][34][35] The effort in this study was aimed to design an efficient and simple synthetic routes for the preparation of pyrimidines and their related fused heterocyclic derivatives, bearing benzo[d] [1,3]dioxole and thiophene moieties as novel antibacterial agents.…”

Utility of 2‐Acetyl Benzofuran for the Synthesis of New Heterocycles as Potential Anticancer Agents

“…On the other hand, literature survey revealed that pyrazoline derivatives possess a broad spectrum of biological activities including anticancer, antiinflammatory, antihypotensive, antidepressant, anticonvulsant, antimicrobial, and antitubercular activities [12][13][14][15][16][17][18]. Moreover, triazolo [4,3-a]pyrimidines has antimicrobial and anticancer [19][20][21] activities. Based on these observations, it was of interest to incorporate benzofuran ring system into different heteroaryl ring systems in one molecule in an attempt to obtain a new target anticancer agents.…”

Synthesis of Some Novel Thiazole, Thiadiazole and 1,4-Phenylene-bis-thiazole Derivatives as Potent Antitumor Agents

“…10,11 In the last two decades we have been involved in a program aiming at the synthesis of functionally substituted heterocyclic compounds from cheap laboratory available starting materials with anticipated biological activities. [12][13][14][15][16][17][18][19][20] Recently, in the frame of our program, some new functionally substituted thiazoles and / or bisthiazoles were required to be screened for their biological activity as antitumor agents. It seemed to us that the combination of a thiazole ring with a pyridine ring in one entity may lead to enhanced biological activity due to the synergistic effect of both rings.…”