- Ultrasound-assisted rapid synthesis of 2-aminopyrimidine and barbituric acid derivatives
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Novel, inexpensive, and relatively expeditious procedure to achieve the synthesis of different 2-aminopyrimidine and barbituric acid derivatives is presented here, starting from readily available compounds such as guanidine hydrochloride, urea, 1,3-dialkylurea, or thiourea. Under ultrasonic irradiation, base-driven (Na2CO3, NaOH, or NaOC2H5) heterocyclization reactions of the aforementioned substrates with diethyl malonate, diethyl-2-alkyl malonate, pentane-2,4-dione, or ethyl-3-oxobutanoate yielded corresponding products. Significant advantages of this sonochemical synthetic protocol with regard to the conventional thermal methods include easy reaction setup and work-up steps, reasonably mild conditions, shorter reaction times (～30 min) and comparably high product yields. The characterization of the synthesized compounds was based on melting points, FT-IR, GC-MS, 1H-NMR techniques, and the obtained data were also checked from the previously published studies.
- Bayramo?lu, Duygu,Kurtay, Gülbin,Güllü, Mustafa
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p. 649 - 658
(2020/02/11)
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- Design and synthesis of some barbituric and 1,3-dimethylbarbituric acid derivatives: A non-classical scaffold for potential PARP1 inhibitors
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Six series based on barbituric acid 5a-e, 10a-d; thiobarbituric acid 6a-e, 11a-d and 1,3-dimethylbarbituric acid 7a-e, 12a-d were prepared and screened for their in vitro PARP1 inhibition. They revealed promising inhibition at nanomolar level especially compounds 5c, 7b, 7d and 7e (IC50 = 30.51, 41.60, 41.53 and 36.33 nM) with higher potency than olaparib (IC50 = 43.59 nM). Moreover, compounds 5b, 5d, 7a, 12a and 12c exhibited good comparable activity (IC50 = 65.93, 58.90, 66.57, 45.40 and 50.62 nM, respectively). Furthermore, the most active compounds 5c, 7b, 7d, 7e, 12a and 12c against PARP1 in vitro were evaluated in the BRCA1 mutated triple negative breast cancer cell line MDA-MB-436 where 5c and 12c showed higher potency compared to olaparib and result in cell cycle arrest at G2/M phase. 5c and 12c showed apoptotic effects in MDA-MB-436 and potentiated the cytotoxicity of temozolomide in A549 human lung epithelial cancer cell line. Compounds 5c and 12c represent interesting starting points towards PARP1 inhibitors.
- Eldin A. Osman, Essam,Hanafy, Noura S.,George, Riham F.,El-Moghazy, Samir M.
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- Synthesis, spectroscopic characterization, computational exploration of 6-(2-(2, 4-dinitrophenylhydrazano)-tetrahydro-2-thioxopyrimidin-4(1h)-one
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The structural and vibrational properties of 6-(2-(2,4-dinitrophenylhydrazano)-tetrahydro-2-thioxopyrimidin-4(1H)-one (3) prepared by condensation of synthesized thiobarbituric acid (1) with 2,4-dinitrophenylhydrazine (2) were studied using experimental F
- Kalaiarasi,Manivarman
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p. 304 - 317
(2017/03/17)
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- Study of solvatochromic behavior and antimicrobial activities of some newly synthesized bis-azo-dapsone congeners
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In the present study, a series of new bisazo dyes derived from dapsone have been synthesized in one step, using diazotized coupling reaction and evaluated for their in-vitro antimicrobial activity. Ampicillin and fluconazole have been taken as reference antibiotics (RA). The structure of synthesized compounds are confirmed by different spectral techniques viz. elemental analysis, 1H NMR, UV-Vis, FT-IR and mass spectrometry. The solvatochromic behavior of the synthesized compounds are also studied by UV-Vis spectrometry. The compound 4b has been observed with significant antibacterial activity against Shigella flexneri, Escherichia coli, Vibrio cholera and Streptococcus mitis in comparison to standard drug whereas all the compounds except 4f show significant antifungal activity against Aspergillus niger. The results have been statistically interpreted by one way analysis-of variance (ANOVA) followed by Dunnett's Post Hoc test. Exploitation of dapsone molecule by the attachment of different nucleophiles may be responsible for the significant increase of antimicrobial activity. However, the 8-hydroxy quinoline linked bisazo dapsone showed highest significant antimicrobial activity than the other newly synthesized bisazo dapsone analogues in comparison to RA.
- Sahoo, Jyotirmaya,Kumar, Paidesetty Sudhir
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p. 724 - 733
(2017/01/18)
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- Synthesis, characterization, solvatochromic properties, and antimicrobial evaluation of 5-acetyl-2-thioxo-dihydro-pyrimidine-4,6-dione-based chalcones
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A new series of chalcone analogs namely 5-(3-phenyl-acryloyl)-2-thioxo- dihydro-pyrimidine-4,6-dione have been synthesized from the key intermediate 5-acetyl-2-thioxo-dihydro-pyrimidine-4,6-dione 4′ with different aldehyde derivatives were performed to get the target compounds as thiobarbituric acid-based chalcones 5(a′-k′) and they were obtained in excellent yields. The newly synthesized compounds were characterized by spectral analysis (FT-IR, 1H NMR, 13C NMR, and UV spectroscopy) and elemental analysis. The synthesized compounds were evaluated for their antimicrobial activity against five bacterial strains (S. aureus, S. pyogenes, E. coli, K. pneumoniae, and P. aeruginosa) and four fungal strains (C. albicans, A. clavatus, T. rubrum, and Penicillium wild strain). Among the screened compounds, 5e′ and f′ showed comparable activity (minimum inhibitory concentration = 500 μg/mL) nearly to that of standard antibiotics griseofulvin.
- Dhorajiya, Bhaveshkumar D.,Bhakhar, Bhimji S.,Dholakiya, Bharatkumar Z.
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p. 4075 - 4086
(2013/09/02)
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- Synthesis, theoretical investigation of 5-(4-dimethylaminobenzylidene) thiobarbituric acid
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In this study, synthesis of 5-benzylidene thiobarbituric acid derivative has been described. The route of preparation involved the uses of thiobarbituric acid as starting material and treated with 4-dimethylaminobenzaldehyde compound to give required derivative. This compound was identified by spectroscopic methods; H NMR, FTIR and CHNS analysis and also by measuring its melting point. A theoretical investigation is performed using hybrid Beck model (B3LYP), ESP showed regular distribution of charge density of whole molecule when one of the two proton is removed from ?-carbon, the ESP for HOMO electron density is heavily localized on α negative carbon, reflect the reactivity of thiobarbituric molecule and show it as highly effective nucleophile when act into nucleophilic substitution reactions.
- Mageed, Ahmed .H.,AL-Ameed, Karrar A.S.
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p. 2953 - 2955
(2013/05/21)
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- 6-Amino-2-mercapto-3H-pyrimidin-4-one derivatives as new candidates for the antagonism at the P2Y12 receptors
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P2Y12 plays an important role in platelet aggregation, which makes it an interesting target for antithrombotic agents. Compounds that antagonize P2Y12 include the active metabolites of thienopyridines and molecules that are structurally related to ATP, which is an antagonist of P2Y12. During the last few years, our group has been working on the development of P2Y12 receptors antagonists that are based on an extremely simple chemical structure, the 6-amino-2-mercapto-3H-pyrimidin-4-one, variously substituted at the sulfur and oxygen functions. This nucleus represents the simplified combination of two known P2Y12 antagonists: the active metabolite of the thienopyridines and ATP derivatives. The effects of the synthesized compounds were tested on ADP-induced human platelet aggregation, using light transmission aggregometry. None of the tested compounds induced platelet aggregation, while some of them, at concentration of 10-4 M, partially inhibited platelet aggregation induced by ADP 10-6 M. The most potent compound, 6b, antagonized the inhibitory effect of 2-methylthio-ADP on the forskolin-induced accumulation of cyclic-AMP in CHO FlpIN cells expressing recombinant human P2Y12-receptors. In addition, none of the tested compounds, including 6b, interfered with ligand binding to P1 receptors. Our results suggest that some of the synthesized compounds are specific antagonists of P2 receptors, and in particular of P2Y12 and suggest that further development of this structurally new series of compounds as P2Y12 receptors antagonists is recommended.
- Crepaldi, Pamela,Cacciari, Barbara,Bonache, Maria-Cruz,Spalluto, Giampiero,Varani, Katia,Borea, Pier Andrea,Kuegelgen, Ivar von,Hoffmann, Kristina,Pugliano, Mariateresa,Razzari, Cristina,Cattaneo, Marco
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experimental part
p. 4612 - 4621
(2009/10/23)
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- Synthesis and anti-HIV-1 activity evaluation of 5-alkyl-2-alkylthio-6- (arylcarbonyl or α-cyanoarylmethyl)-3,4-dihydropyrimidin-4(3H)-ones as novel non-nucleoside HIV-1 reverse transcriptase inhibitors
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A series of novel S-DABO analogues (S-DABOs, 1) were synthesized and evaluated as inhibitors of human immunodeficiency virus type-1 (HIV-1). Key structural modifications included replacement of the 6-arylmethyl group by a 6-arylcarbonyl or 6-(α-cyanoarylmethyl) group. Most of the compounds showed only micromolar potency against HIV-1 in MT-4 cells in vitro, though two of them (3e and 3g) were unusually potent (IC50 = 0.09 and 0.002 μM, respectively) and selective (SI = 1500 and 4600, respectively). Structure-activity relationships among the newly synthesized S-DABOs are discussed.
- Ji, Lei,Chen, Fen-Er,De Clercq, Erik,Balzarini, Jan,Pannecouque, Christophe
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p. 1778 - 1786
(2008/02/01)
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- Discovery of inhibitors of the pentein superfamily protein dimethylarginine dimethylaminohydrolase (DDAH), by virtual screening and hit analysis
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An efficient process for the discovery of inhibitors of DDAH enzymes, without the requirement for high throughput screening, is described. Physicochemical filtering of a 308,000-compound library according to drug likeness followed by reciprocal nearest neighbour selection produced a representative subset of 35,000 compounds. Virtual screening on a dual processor PC using FlexX, followed by biological screening, identified two hit series. Similarity searches of commercial databases and chemical re-synthesis of pure compounds resulted in SR445 as an inhibitor of Pseudomonas aeruginosa DDAH at 2 μM.
- Hartzoulakis, Basil,Rossiter, Sharon,Gill, Herpreet,O'Hara, Bernard,Steinke, Emily,Gane, Paul J.,Hurtado-Guerrero, Ramon,Leiper, James M.,Vallance, Patrick,Rust, Judith Murray,Selwood, David L.
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p. 3953 - 3956
(2008/09/16)
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- Chemical modification of plant alkaloids. 2. Reaction of cotarnine with barbituric acid derivatives and structure of 5-dihydrocotarnylbarbituric acids
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The reaction of barbituric acid and its N-substituted derivatives and 2-thio analogs with cotarnine forms 5-(4-methoxy-6-methyl-5,6,7,8-tetrahydro-2H-1,3-methylenedioxy-[4,5-g]isoquinolinyl-1)barbituric acids, a new class of zwitter-ions, the structure of which was studied by 1H and 13C NMR spectroscopy and mass spectrometry. The prepared compounds exist in solution as stable intermolecular associates and have a complicated H-bonded structure.
- Krasnov,Kartsev,Yurova
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p. 543 - 550
(2007/10/03)
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- Oxo propenyl nucleosides and nucleoside related analogs
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Certain 3-oxo-prop-1-enyl purine and pyrimidine derivatives and the corresponding nucleosides have been prepared. These compounds exhibit interesting and valuable cytotoxic activity. This cytotoxicity is of special interest in that it appears to inhibit DNA reproduction without affecting RNA or protein synthesis.
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- A C-13 nuclear magnetic resonance study of the pyrimidine synthesis by the reactions of 1,3-dicarbonyl compounds with amidines and ureas
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The detailed mechanistic pathways are elucidated for the reactions of acetylacetone, methyl acetoacetate, and dimethyl malonate with a variety of amidines and ureas.In many cases the identification of a single intermediate allows the definition of the reaction path and identification of two steps.Intermediates characterized include ring-closed dihydroxytetrahydropyrimidines, dihydrohydroxypyrimidinones, open-chain enamides, and carbonyl addition compounds.
- Katritzky, Alan R.,Yousaf, Taher I.
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p. 2087 - 2093
(2007/10/02)
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- Metal complexes of azomethines and process for their manufacture
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Metal complexes of azomethines of the formula STR1 are useful for coloring plastics and lacquers in yellow to red shades of excellent fastness properties.
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