6642-31-5Relevant articles and documents
Spectrophotometric investigation of 5-nitroso-6-aminouracil and its methyl derivative in methanol by selective complexation with bivalent metal ions
Das, Subrata,Hussain, Sahid,Kumar, Brajesh,Kumar, Pramanand,Sugunakara Rao, Mugada
, (2020/07/20)
6-Amino-5-nitrosouracils are synthesized by the condensation reaction of urea or N,N′-dimethyl urea, cyanoacetic acid and acetic anhydride followed by nitrosation reaction with sodium nitrite. The synthesized compounds are characterized by various spectroscopic techniques like FTIR, NMR, single crystal XRD, and UV–vis absorption spectroscopy. From a single-crystal X-ray crystallography study of DANU, it is found that the compound is crystalline with one water molecule. The binding properties of both compounds with various metal ions are studied using UV–vis spectroscopy, where ANU shows a colour change from colourless to yellow colour-forming complex with cobalt metal ion. While DANU shows a colour change from colourless to dark yellow forming complex with copper and nickel cation, respectively. These compounds showed the job's plots with Cu2+, Ni2+, and Co2+ in various stoichiometric ratios to form the respective metal complex. The association/binding constant (Ka) values are calculated by plotting Benesi–Hilderbrand plots of ANU with Co2+ ion and is found to be 9.524 × 102. Whereas, DANU with Cu2+, Ni2+ are found to be 3.956 × 103, 2.041 × 103, respectively. These cations may be used in metal ions complexation for the respective ligand. The LOD values for ANU-Co2+, DANU-Cu2+ & DANU-Ni2+ are obtained as 33.9428 μM, 93.8082 μM and 48.396 μM, respectively, whereas the LOQ values are found as 102.857 μM, 284.2675 μM and 146.653 μM, respectively.
Synthesis method of theophylline
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Paragraph 0030; 0031; 0034; 0035; 0038; 0039; 0042-0045, (2020/12/29)
The invention discloses a synthesis method of theophylline, and relates to the technical field of preparation of heterocyclic compounds containing purine ring systems. The preparation method comprisesthe following steps: mixing cyanoacetic acid and acetic anhydride at 30-80 DEG C for reaction, adding a solvent and dimethylurea, cooling to room temperature after reflux reaction is finished, filtering, concentrating filtrate, combining solids to obtain dimethylacetamide, adding liquid caustic soda to adjust the pH to 8-11, and reacting at 80-100 DEG C to generate dimethyl 4AU; completely dissolving dimethyl 4AU in formic acid, adding sodium nitrite, reacting at room temperature, adding a catalyst and water, keeping the temperature at 30-70 DEG C, recovering the catalyst after the reaction is finished, and concentrating mother liquor to recover formic acid, thereby obtaining dimethyl FAU; adding dilute sulfuric acid into the dimethyl FAU to adjust the pH value to 36, heating to 90-100 DEG C, allowing the feed liquid to pass through an ozone reactor and a decolorizer, crystallizing by a crystallizer, and carrying out cold filtration to obtain theophylline. The method has the advantages of few reaction steps, mild reaction conditions, simple operation, high yield, stable product quality, small discharge capacity, reduction of the environmental protection treatment difficulty, and easy industrialization.
Pyrimidopteridine N-Oxide Organic Photoredox Catalysts: Characterization, Application and Non-Covalent Interaction in Solid State
Hauptmann, Richy,Petrosyan, Andranik,Fennel, Franziska,Argüello Cordero, Miguel A.,Surkus, Annette-E.,Pospech, Jola
supporting information, p. 4325 - 4329 (2019/03/29)
Herein we report the photo- and electrochemical characterization of pyrimidopteridine N-oxide-based heterocycles. The potential of their application as organic photoredox catalysts is showcased in the photomediated contra-thermodynamic E→Z isomerization of cinnamic acid derivatives and oxidative cyclization of 2-phenyl benzoic acid to benzocoumarin using molecular oxygen as a mild oxidant. Furthermore, unprecedented intermolecular non-covalent n–π-hole interactions in solid state are discussed based on crystallographic and theoretical data.
Selective Inhibitors of a Human Prolyl Hydroxylase (OGFOD1) Involved in Ribosomal Decoding
Thinnes, Cyrille C.,Lohans, Christopher T.,Abboud, Martine I.,Yeh, Tzu-Lan,Tumber, Anthony,Nowak, Rados?aw P.,Attwood, Martin,Cockman, Matthew E.,Oppermann, Udo,Loenarz, Christoph,Schofield, Christopher J.
supporting information, p. 2019 - 2024 (2019/01/11)
Human prolyl hydroxylases are involved in the modification of transcription factors, procollagen, and ribosomal proteins, and are current medicinal chemistry targets. To date, there are few reports on inhibitors selective for the different types of prolyl hydroxylases. We report a structurally informed template-based strategy for the development of inhibitors selective for the human ribosomal prolyl hydroxylase OGFOD1. These inhibitors did not target the other human oxygenases tested, including the structurally similar hypoxia-inducible transcription factor prolyl hydroxylase, PHD2.
Structural and conformational studies on carboxamides of 5,6-diaminouracils-precursors of biologically active xanthine derivatives
Marx, Daniel,Schnakenburg, Gregor,Grimme, Stefan,Müller, Christa E.
supporting information, (2019/06/21)
8-Arylethynylxanthine derivatives are potent, selective adenosine A2A receptor antagonists, which represent (potential) therapeutics for Parkinson's disease, Alzheimer's dementia, and the immunotherapy of cancer. 6-Amino-5-amidouracil derivatives are important precursors for the synthesis of such xanthines. We noticed an unexpected duplication of NMR signals in many of these uracil derivatives. Here, we present a detailed analytical study of structurally diverse 6-amino-5-carboxamidouracils employing dynamic and two-dimensional NMR spectroscopy, density functional theory calculations, and X-ray analysis to explain the unexpected properties of these valuable drug intermediates.
Synthesis and biological evaluation of novel xanthine derivatives as potential apoptotic antitumor agents
Hisham, Mohamed,Youssif, Bahaa G.M.,Osman, Essam Eldin A.,Hayallah, Alaa M.,Abdel-Aziz, Mohamed
, p. 117 - 128 (2019/05/21)
A series of novel xanthine/NO donor hybrids containing 1,3,8-trisubstituted or 1,8-disubstituted xanthine derivatives were designed and synthesized. The synthesized compounds were tested in a cell viability assay using human mammary gland epithelial cell line (MCF-10A) where all the compounds exhibited no cytotoxic effects and more than 90% cell viability at a concentration of 50 μM. The oxime containing compounds 7a-b and 17-24 were more active as antiproliferative agents than their non-oxime congeners 6a-b and 9-16. Hydroxyimino-phenethyl scaffold compounds 17-24 were more active than the hydroxyimino-ethyl phenyl acetamide 7a-b derivatives. Compounds 18–20 and 22-24 exhibited inhibition of EGFR with IC50 ranging from 0.32 to 2.88 μM. Compounds 18-20 and 22-24 increased the level of active caspase 3 by 4–8 folds, compared to the control cells in Panc-1 cell lines compared to doxorubicin as a reference drug. Compounds 18, 22 and 23 were the most caspase-3 inducers. Compounds 22 and 23 increased the levels of caspase-8 and 9 indicating activation of both intrinsic and extrinsic pathways and showed potent induction of Bax, down-regulation of Bcl-2 protein levels and over-expression of cytochrome c levels in Panc-1 human pancreas cancer cells. Compound 23 exhibited mainly cell cycle arrest at the Pre-G1 and G2/M phases in the cell cycle analysis of Panc-1 cell line. The drug likeness profiles of compounds 18-20 and 22-24 were predicted to have good to excellent drug likeness profiles specially compounds 18-20 and 23. Finally molecular docking study was performed at the EGFR active site to suggest thier possible binding mode. The hydroxyimino-phenethyl scaffold compounds 17-24 represent an interesting starting point to optimize their pharmacokinetics and pharmacodynamics profiles.
EGFR inhibitors and apoptotic inducers: Design, synthesis, anticancer activity and docking studies of novel xanthine derivatives carrying chalcone moiety as hybrid molecules
Abou-Zied, Hesham A.,Youssif, Bahaa G.M.,Mohamed, Mamdouh F.A.,Hayallah, Alaa M.,Abdel-Aziz, Mohamed
, (2019/05/29)
One of the helpful ways to improve the effectiveness of anticancer agents and weaken drug resistance is to use hybrid molecules. therefore, the current study intended to introduce 20 novel xanthine/chalcone hybrids 9–28 of promising anticancer activity. Compounds 10, 11, 13, 14, 16, 20 and 23 exhibited potent inhibition of cancer cells growth with IC50 ranging from 1.0 ± 0.1 to 3.5 ± 0.4 μM compared to doxorubicin with IC50 ranging from 0.90 ± 0.62 to 1.41 ± 0.58 μM and that compounds 11 and 16 were the best. To verify the mechanism of their anticancer activity, compounds 10, 11, 13, 14, 16, 20 and 23 were evaluated for their EGFR inhibitory effect. The study results revealed that compound 11 showed IC50 = 0.3 μM on the target enzyme which is more potent than staurosporine reference drug (IC50 = 0.4 μM). Accordingly, the apoptotic effect of the most potent compounds 11 was extensively investigated and showed a marked increase in Bax level up to 29 folds, and down-regulation in Bcl2 to 0.28 fold, in comparison to the control. Furthermore, the effect of compound 11 on Caspases 3 and 8 was evaluated and was found to increase their levels by 8 and 14 folds, respectively. Also, the effect of compound 11 on the cell cycle and its cytotoxic effect were examined. Moreover, a molecular docking study was adopted to confirm mechanism of action.
Iodine/persulfate-promoted site-selective direct thiolation of quinolones and uracils
Beukeaw, Danupat,Noikham, Medena,Yotphan, Sirilata
supporting information, (2019/09/03)
A simple and general method for direct thiolation of 4-quinolones with disulfides or thiols under I2/K2S2O8 system has been developed. Under the optimal conditions, the C–S bond coupling can take place effectively with good to decent yields and excellent regioselectivity of the S-linked products. The established metal-free site-selective approach was also applicable to transform a range of uracil substrates to the thio-substituted products under mild conditions. Further transformation to the sulfone derivatives can be conveniently performed in one-pot. These easy-to-handle protocols represent a useful and interesting synthetic alternative with good substrate scope and functional group compatibility.
Synthesis and Evaluation of a New Series of 8-(2-Nitroaryl)Xanthines as Adenosine Receptor Ligands
Bansal, Ranju,Kumar, Gulshan,Rohilla, Suman,Klotz, Karl-Norbert,Kachler, Sonja,Young, Louise C.,Harvey, Alan L.
, p. 241 - 250 (2016/08/28)
(Table presented.). A new series of 1,3-dimethylxanthine derivatives bearing 8-(2-nitroaryl) residue was synthesized and evaluated for affinity for recombinant human adenosine receptors subtypes. Nitrate esters of 7-substituted-1,3-dimethyl-8-phenylxanthines were also synthesized and tested. Introducing a nitro substituent at the 2-position of the 8-substituted phenyl ring resulted in generally low affinity for adenosine receptors (ARs), selectivity toward the A2A subtype was enhanced in some of the compounds. 8-(4-Cyclopentyloxy-5-methoxy-2-nitrophenyl)-1,3-dimethylxanthine (9e) proved to be a potent compound among the 2-nitrophenyl substituted xanthines exhibiting a Ki = 1 μM at human A2A ARs with at least 30 fold selectivity versus human A1 and A2B ARs. Replacement of 8-chloropropoxy phenyl with 8-nitrooxypropoxy phenyl resulted in a negligible change in binding affinity of the 8-substituted xanthines for various AR subtypes. Drug Dev Res 77 : 241–250, 2016.
A method of preparing high-purity theophylline
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Paragraph 0026; 0027; 0028, (2017/02/02)
The invention discloses a method for preparing high-purity theophylline. The method comprises the following steps: performing a methylation reaction of 6-aminouracil, dimethyl sulfoxide, sodium hydride and methyl iodide; adding formic acid for a carboxylation reaction; adding a mixed acid solution formed by mixing fuming nitric acid and concentrated sulfuric acid, and performing heating reflux for a nitrosylation reaction; and finally, adding iron powder and anhydrous acetic acid for a cyclization reaction to obtain theophylline. According to the method disclosed by the invention, the technology is simple, the requirements on the reaction conditions are low, the yield is increased over the prior art, and the obtained theophylline has high purity.
