60045-65-0Relevant articles and documents
Trisubstituted barbiturates and thiobarbiturates: Synthesis and biological evaluation as xanthine oxidase inhibitors, antioxidants, antibacterial and anti-proliferative agents
Figueiredo, Joana,Serrano, Jo?o L.,Cavalheiro, Eunice,Keurulainen, Leena,Yli-Kauhaluoma, Jari,Moreira, Vania M.,Ferreira, Susana,Domingues, Fernanda C.,Silvestre, Samuel,Almeida, Paulo
, p. 829 - 842 (2017/12/13)
Barbituric and thiobarbituric acid derivatives have become progressively attractive to medicinal chemists due to their wide range of biological activities. Herein, different series of 1,3,5-trisubstituted barbiturates and thiobarbiturates were prepared in moderate to excellent yields and their activity as xanthine oxidase inhibitors, antioxidants, antibacterial agents and as anti-proliferative compounds was evaluated in vitro. Interesting bioactive barbiturates were found namely, 1,3-dimethyl-5-[1-(2-phenylhydrazinyl)ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6c) and 1,3-dimethyl-5-[1-[2-(4-nitrophenyl)hydrazinyl]ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6e), which showed concomitant xanthine oxidase inhibitory effect (IC50 values of 24.3 and 27.9 μM, respectively), and 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity (IC50 values of 18.8 and 23.8 μM, respectively). In addition, 5-[1-(2-phenylhydrazinyl)ethylidene]pyrimidine-2,4,6(1H,3H,5H)-trione (6d) also revealed DPPH radical scavenger effect, with an IC50 value of 20.4 μM. Moreover, relevant cytotoxicity against MCF-7 cells (IC50 = 13.3 μM) was observed with 5-[[(2-chloro-4-nitrophenyl)amino]methylene]-2-thioxodihydropyrimidine-4,6(1H,5H)-dione (7d). Finally, different 5-hydrazinylethylidenepyrimidines revealed antibacterial activity against Acinetobacter baumannii (MIC values between 12.5 and 25.0 μM) which paves the way for developing new treatments for infections caused by this Gram-negative coccobacillus bacterium, known to be an opportunistic pathogen in humans with high relevance in multidrug-resistant nosocomial infections. The most promising bioactive barbiturates were studied in silico with emphasis on compliance with the Lipinski's rule of five as well as several pharmacokinetics and toxicity parameters.
A synthetic route to novel 3-substituted-2,1-benzisoxazoles from 5-(2-nitrobenzylidene)(thio)barbiturates
Serrano, Jo?o L.,Cavalheiro, Eunice,Barroso, Sónia,Rom?o, Maria J.,Silvestre, Samuel,Almeida, Paulo
, p. 990 - 995 (2017/11/27)
2,1-Benzisoxazoles, also called anthranils, are one of the two types of aromatic bicyclic heterocycles having a benzene ring fused with an isoxazole, which are particularly recognized as valuable intermediates in organic synthesis. Nevertheless several methods can be found in the literature to prepare 2,1-benzisoxazoles, we herein report a new, efficient, simple, mild, and alternative procedure to prepare 3-substituted-2,1-benzisoxazoles from 5-(2-nitrobenzylidene)barbiturates in moderate to good yields (51–82%). All the novel benzisoxazoles showed spectral data fully consistent with the assigned structures, which were unequivocally confirmed by single crystal X-ray analysis. A possible mechanism of the reaction is proposed. In addition, a screening of the bioactivity of these benzisoxazoles as xanthine oxidase inhibitors, antioxidants, and cytotoxic compounds was performed. The benzisoxazole formed from barbituric acid revealed moderate xanthine oxidase inhibitory effects (IC50 = 22.10 μM).
New strategy for the synthesis of 5-Aryl-1H,1′H-spiro[furo[2,3-d] pyrimidine-6,5′-pyrimidine]2,2′,4,4′,6′(3H,3'H,5H) -pentaones and their sulfur analogues
Jalilzadeh, Mohammad,Pesyan, Nader Noroozi
experimental part, p. 3382 - 3388 (2012/01/19)
Reaction of barbituric acid (BA), 1,3-dimethyl barbituric acid (DMBA) and 2-thiobarbituric acid (TBA) with cyanogen bromide and aldehydes in the presence of L-(+)-tartaric acid afforded a new route for the synthesis of stable heterocyclic 5-aryl-1H,1′H-spiro[furo[2,3-d]pyrimidine-6,5′- pyrimidine]2,2′,4,4′,6′(3H,3′H,5H)- pentaones which is a dimeric form of barbiturate (uracil and thiouracil derivative). In the reaction of 1,3-diethyl thiobarbituric acid (DETBA) the Knoevenagel condensation and then Michael adducts were obtained under the same condition. Structure elucidation is carried out by 1H NMR, 13C NMR, FT-IR and Mass analyses. Mechanism of the formation is discussed.
