- Synthesis, radiolabelling and initial biological characterisation of 18F-labelled xanthine derivatives for PET imaging of Eph receptors
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Eph receptor tyrosine kinases, particularly EphA2 and EphB4, represent promising candidates for molecular imaging due to their essential role in cancer progression and therapy resistance. Xanthine derivatives were identified to be potent Eph receptor inhibitors with IC50 values in the low nanomolar range (1-40 nm). These compounds occupy the hydrophobic pocket of the ATP-binding site in the kinase domain. Based on lead compound 1, we designed two fluorine-18-labelled receptor tyrosine kinase inhibitors ([18F]2/3) as potential tracers for positron emission tomography (PET). Docking into the ATP-binding site allowed us to find the best position for radiolabelling. The replacement of the methyl group at the uracil residue ([18F]3) rather than the methyl group of the phenoxy moiety ([18F]2) by a fluoropropyl group was predicted to preserve the affinity of the lead compound 1. Herein, we point out a synthesis route to [18F]2 and [18F]3 and the respective tosylate precursors as well as a labelling procedure to insert fluorine-18. After radiolabelling, both radiotracers were obtained in approximately 5% radiochemical yield with high radiochemical purity (>98%) and a molar activity of >10 GBq μmol-1. In line with the docking studies, first cell experiments revealed specific, time-dependent binding and uptake of [18F]3 to EphA2 and EphB4-overexpressing A375 human melanoma cells, whereas [18F]2 did not accumulate at these cells. Since both tracers [18F]3 and [18F]2 are stable in rat blood, the novel radiotracers might be suitable for in vivo molecular imaging of Eph receptors with PET.
- Belter, Birgit,Caflisch, Amedeo,K?ckerling, Martin,Kinski, Elisa,Mamat, Constantin,Neuber, Christin,Pietzsch, Jens,Pretze, Marc,Steinbach, J?rg
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- 3-Substituted xanthines as promising candidates for quadruplex formation: Computational, synthetic and analytical studies
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Our computational studies suggest that 3-substituted xanthines are good candidates for tetrad and quadruplex structures. 3-Methylxanthine (3MX) has been synthesized from 7-benzylxanthine, and the existence of tetrameric and octameric aggregates of 3MX with NH4+, Na+ and K+ ions in the gas phase (MS) and in DMSO-d6 solution (NMR) has been observed. The "internal" H-bonds (N1H...O6) are stronger than the "external" ones (N7H...O2) in these clusters (NMR).
- Szolomajer, Janos,Paragi, Gabor,Batta, Gyula,Guerra, Celia Fonseca,Bickelhaupt, F. Matthias,Kele, Zoltan,Padar, Petra,Kupihar, Zoltan,Kovacs, Lajos
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- Inhibition kinetics of theophylline metabolism by mexiletine and its metabolites
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To further characterize the mode of drug interaction between theophylline (TP) and mexiletine (ME), in vitro kinetic studies were carried out using rat liver microsomes and 9000 x g supernatant. The kinetic study revealed that the K, value and V(max)/K(m) ratio for the metabolic conversion of TP to 1,3-dimethyluric acid (1,3-DMU) were the second lowest and the highest, respectively, of four metabolic pathways. Thus, the rank of efficiency of the oxidative metabolism by microsomal cytochrome P-450 (P-450) isozymes was TP to 1,3-DMU > TP to 1-methylxanthine (1-MX) > TP to 3-MX > 1,3-DMU to 1-methyluric acid, suggesting that the isozyme metabolizing TP would have a higher affinity for the oxidation at the 8-position in TP molecules than at the 1- and 3-positions. Lineweaver-Burk plots showed that the conversion of TP to 3-MX and to 1,3-DIMU was inhibited competitively by ME and its metabolites, and that the pathway of TP to 1-MX was inhibited noncompetitively. In consideration of the K(i) values calculated, it seems probable that deamino-p-hydroxy ME (DApHME) might be the most potent inhibitor of the metabolic pathways of TP, and that the rank order of inhibition is approximately DApHME > p-hydroxy ME > deamino-hydroxymethyl ME > ME > hydroxymethyl ME, with some exceptions. The mechanism of the interaction between TP and ME is probably due to the metabolic antagonism in the liver, and TP, ME and their metabolites share' some of the same metabolic pathways, mediated by P-450 isozymes.
- Ogiso,Iwaki,Uno
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- Synthesis and bio-evaluation of a novel selective butyrylcholinesterase inhibitor discovered through structure-based virtual screening
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In recent years, butyrylcholinesterase (BChE) has gradually gained worldwide interests as a novel target for treating Alzheimer's disease (AD). Here, two pharmacophore models were generated using Schr?dinger suite and used to virtually screen ChemDiv database, from which three hits were obtained. Among them, 2513–4169 displayed the highest inhibitory activity and selectivity against BChE (eeAChE IC50 > 10 μM, eqBChE IC50 = 3.73 ± 1.90 μM). Molecular dynamic (MD) simulation validated the binding pattern of 2513–4169 in BChE, and it could form a various of receptor-ligand interactions with adjacent residues. In vitro cytotoxicity assay proved the safety of 2513–4169 on diverse neural cell lines. Moreover, the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay performed on SH-SY5Y cells proved the neuroprotective effect of 2513–4169 against toxic Aβ1–42. In vivo behavioral study further confirmed the great efficacy of 2513–4169 on reversing Aβ1–42-induced cognitive impairment of mice and clearing the toxic Aβ1–42 in brains. Moreover, 2513–4169 was proved to be able to cross blood-brain barrier (BBB) through a parallel artificial membrane permeation assay of BBB (PAMPA-BBB). Taken together, 2513–4169 is a promising lead compound for future optimization to discover anti-AD treating agents.
- Chen, Yao,Chen, Ying,Feng, Feng,Jiao, Mengxia,Li, Qi,Liu, Wenyuan,Lu, Weixuan,Sun, Haopeng,Wang, Yuanyuan,Xing, Shuaishuai,Xiong, Baichen
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- Characterization of Human Cytochromes P450 Involved in Theophylline 8-Hydroxylation
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Studies were undertaken to determine which human P450 enzymes catalyze the metabolism of theophylline to 1,3-dimethyluric acid (1,3-DU), to facilitate predictions of theophylline drug-drug interactions, and to develop a noninvasive test for human P4501A2. Microsomes from a human cell line transfected individually with human P450 cDNAs for P4501A1, 1A2, 2A6, 2B6, 2C9, 2D6, 2E1, or 3A4 were used to demonstrate that only P4501A2 exhibited catalytic activity for theophylline metabolism to 1,3-DU with high affinity and low capacity (Km = 0.6 mM, Vmax = 37.8, pmol/min/mg), while P4502D6, 2E1, and 3A4 (Km = 14.4, 19.9, and 25.1 mM, respectively, and Vmax = 219.8, 646.4, and 20.8 pmol/min/mg, respectively) exhibited activities with low affinity and variable capacities. Correlations of rates of theophylline 8-hydroxylation to 1,3-DU with other P450 form-specific activities, in a series of ten human liver microsomal preparations, at 5 and 40 mM theophylline concentrations, revealed that at low concentrations the metabolism was catalyzed primarily by P4501A2, while at high substrate concentrations P4502E1 was primarily responsible for catalysis. The results with individually expressed P450s and hepatic microsomal preparations were consistent, indicating that the former system provides a qualitatively accurate reflection of the function of the heterogeneously expressed liver P450s. At pharmacologic theophylline concentrations achieved in vivo, its metabolism must thus be catalyzed primarily by P4501A2.
- Zhang, Zhi-Yi,Kaminsky, Laurence S.
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- Multiplicity of cytochrome P-450 species involved in theophylline metabolism in mouse hepatic microsomes
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To ascertain the multiplicity of the cytochrome P-450 (P-450) species participating in the individual metabolic conversion of theophylline by 8-hydroxylation, 3-demethylation and 1-demethylation in mice, kinetics were studied under various conditions using untreated and inducer-treated mouse hepatic microsomes. Eadie-Hofstee plots of 1-demethylation in untreated microsomes exhibited a straight line, whereas those of 8-hydroxylation and 3-demethylation were curved lines. The biphasic kinetics indicated the contribution of two P-450 populations to the respective metabolic pathways; one characterized by high affinity and low capacity, the other by low affinity and high capacity. The high affinity population was efficiently induced by β-naphthoflavone (β-NF), and was highly susceptible to inhibition by a specific CYP1A inhibitor. The low affinity population was sensitive to induction by phenobarbital (PB), and was markedly inhibited by preferential inhibitors for PB-inducible P-450 species. The present results indicated that two P-450 populations contributed to the theophylline metabolism in mouse hepatic microsomes, and that the high and low affinity populations corresponded, respectively, to CYP1A, and a PB-inducible P-450 species having a much higher capacity than CYP1A.
- Konishi,Morita,Yamaji
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- Novel, Dual Target-Directed Annelated Xanthine Derivatives Acting on Adenosine Receptors and Monoamine Oxidase B
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Annelated purinedione derivatives have been shown to act as possible multiple-target ligands, addressing adenosine receptors and monoaminooxidases. In this study, based on our previous results, novel annelated pyrimido- and diazepino[2,1-f]purinedione derivatives were designed as dual-target-directed ligands combining A2A adenosine receptor (AR) antagonistic activity with blocking monoamine oxidase B. A library of 19 novel compounds was synthesized and biologically evaluated in radioligand binding studies at AR subtypes and for their ability to inhibit MAO-B. This allowed 9-(2-chloro-6-fluorobenzyl)-3-ethyl-1-methyl-6,7,8,9-tetrahydropyrimido[2,1-f]purine-2,4(1H,3H)-dione (13 e; Ki human A2AAR: 264 nM and IC50 human MAO-B: 243 nM) to be identified as the most potent dual-acting ligand from this series. ADMET parameters were estimated in vitro, and analysis of the structure-activity relationships was complemented by molecular-docking studies based on previously published X-ray structures of the protein targets. Such dual-acting ligands, by selectively blocking A2A AR, accompanied by the inhibition of dopamine metabolizing enzyme MAO-B, might provide symptomatic and neuroprotective effects in, among others, the treatment of Parkinson disease.
- Brockmann, Andreas,Doroz-P?onka, Agata,Ja?ko, Piotr,Kie?-Kononowicz, Katarzyna,Kuder, Kamil J.,Latacz, Gniewomir,Müller, Christa E.,Olejarz-Maciej, Agnieszka,Schabikowski, Jakub,Za?uski, Micha?
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- Preparation method of hypoglycemic drug linagliptin intermediate
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The invention provides a preparation method of a hypoglycemic drug linagliptin intermediate, wherein the method comprises the steps: in the presence of a catalyst and an organic solvent, carrying out condensation reaction on o-aminoacetophenone (1) and 2-chloroacetamide (2) to obtain an intermediate II; carrying out condensation, bromination, substitution and other reactions on 4-(methylamino)-1H-imidazol-5-carboxamide (3) to generate an intermediate III; and finally, carrying out alkylation reaction on the intermediate II and the intermediate III to generate an intermediate I. According to the preparation method, generation of side reactions are avoided. Moreover, the reaction cost is saved, the operation conditions are mild, the yield is high, the post-treatment is simple, and the method is suitable for industrial large-scale production.
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Paragraph 0049-0057
(2021/04/21)
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- Linagliptin intermediate compound IV
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The invention belongs to the field of pharmaceutical chemicals, and discloses a linagliptin intermediate IV and a novel route for synthesizing an important linagliptin intermediate from the linagliptin intermediate IV. The linagliptin intermediate IV synthesized in the invention has the advantages of high yield, simple operation, substantial reduction of production cost, suitableness for industrial production; and the synthesis route solves the problems of self-coupling of linagliptin intermediates and generation of large impurities in the prior art.
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Paragraph 0188; 0192
(2020/09/09)
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- Linagliptin intermediate compound V
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The invention belongs to the field of pharmaceutical chemicals, and provides a linagliptin intermediate compound V and an important intermediate for synthesizing linagliptin by using the intermediateV. The method solves the problems of self-coupling of linagliptin intermediates and generation of large impurities in the prior art, and the synthesized novel intermediate compound V has the advantages of high yield, simple operation, significantly reduced production cost, and suitableness for industrial production.
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Paragraph 0185; 0189; 0196; 0199
(2020/09/09)
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- Preparation method of theobromine
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The invention discloses a preparation method of theobromine, and relates to the technical field of preparation of heterocyclic compounds containing purine ring systems. The method comprises the following steps: adding oxalyl chloride into cyanoacetic acid and a solvent at the temperature of -10-20 DEG C, concentrating to remove the solvent and oxalyl chloride after reaction, adding monomethylureaand the solvent at the temperature of 0-30 DEG C, adding alkali as an acid-binding agent, adding water after reaction, stirring, and filtering to obtain monomethyl cyanoacetylurea; adding water to dissolve cyanuric chloride, adding liquid caustic soda to adjust the pH value to 8-11, and reacting at 80-100 DEG C to generate methyl 4AU; dissolving monomethyl 4AU in formic acid, adding sodium nitrite, reacting at room temperature, adding a catalyst, 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 monomethyl FAU; adding water and liquid caustic soda into monomethyl FAU, carrying out ring-closure reaction, and then adding acid to adjust to be neutral, so as to obtain 3-methyl xanthine; and carrying out a methylation reaction on 3-methylxanthine, and refining to obtain theobromine. The method has the advantages of few reaction steps, few side reactions, high yield and stable product quality.
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- Substituted xanthine compound and its preparation and use (by machine translation)
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The invention discloses substituted xanthine compounds, a preparation method and applications thereof, and specifically relates to compounds represented by the formula (I), stereo isomers and pharmaceutically acceptable salts thereof, wherein the R1 and R2 are defined in the description. The invention also relates to a pharmaceutical composition containing the compounds, an application of the pharmaceutical composition in preparation of drugs for treating diseases or symptoms caused by high activity of DPP-IV or overexpression of DPP-IV, and a method using the pharmaceutical composition to treat related diseases. The provided compounds can effectively inhibit the activity of DPP-IV.
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Paragraph 0173; 0174; 0181; 0182
(2018/09/26)
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- Xanthine compound and pharmaceutical composition and application thereof
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The invention discloses a xanthine derivative as shown in the formula (I) and a pharmaceutical composition and application thereof. The xanthine derivative is prepared from a compound as shown in theformula (I) or a stereoisomer, a geometrical isomer, a hydrate or a solvate thereof, or a pharmaceutically acceptable salt or prodrug as shown in the description. The invention also relates to application of the compound as shown in the formula (I) and the pharmaceutical composition thereof as a DPP-4 inhibitor, and especially application in preparation of medicines for treating and/or preventingmetabolic disorder diseases such as diabetes.
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Paragraph 0142; 0149; 0150
(2019/07/11)
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- Hydroxyl radical induced oxidation of theophylline in water: A kinetic and mechanistic study
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Oxidative destruction and mineralization of emerging organic pollutants by hydroxyl radicals (OH) is a well established area of research. The possibility of generating hazardous by-products in the case of OH reaction demands extensive investigations on the degradation mechanism. A combination of pulse radiolysis and steady state photolysis (H2O2/UV photolysis) followed by high resolution mass spectrometric (HRMS) analysis have been employed to explicate the kinetic and mechanistic features of the destruction of theophylline, a model pharmaceutical compound and an identified pollutant, by OH in the present study. The oxidative destruction of this molecule, for intermediate product studies, was initially achieved by H2O 2/UV photolysis. The transient absorption spectrum corresponding to the reaction of OH with theophylline at pH 6, primarily caused by the generation of (T8-OH), was characterised by an absorption band at 330 nm (k2 = (8.22 ± 0.03) × 109 dm3 mol-1 s-1). A significantly different spectrum (λmax: 340 nm) was observed at highly alkaline pH (10.2) due to the deprotonation of this radical (pKa ~ 10.0). Specific one electron oxidants such as sulphate radical anions (SO4-) and azide radicals (N 3) produce the deprotonated form (T(-H)) of the radical cation (T+) of theophylline (pKa 3.1) with k2 values of (7.51 ± 0.04) × 109 dm3 mol-1 s-1 and (7.61 ± 0.02) × 109 dm3 mol-1 s-1 respectively. Conversely, oxide radicals (O -) react with theophylline via a hydrogen abstraction protocol with a rather slow k2 value of (1.95 ± 0.02) × 109 dm3 mol-1 s-1. The transient spectral studies were complemented by the end product profile acquired by HRMS analysis. Various transformation products of theophylline induced by OH were identified by this technique which include derivatives of uric acids (i, iv & v) and xanthines (ii, iii & vi). Further breakdown of the early formed product due to OH attack leads to ring opened compounds (ix-xiv). The kinetic and mechanistic data furnished in the present study serve as a basic frame work for the construction of OH induced water treatment systems as well as to understand the biological implications of compounds of this kind. the Partner Organisations 2014.
- Sunil Paul,Aravind,Pramod,Saha,Aravindakumar
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p. 5611 - 5620
(2014/07/22)
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- Structure-based optimization of potent and selective inhibitors of the tyrosine kinase erythropoietin producing human hepatocellular carcinoma receptor B4 (EphB4)
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The tyrosine kinase EphB4 is an attractive target for drug design because of its recognized role in cancer-related angiogenesis. Recently, a series of commercially available xanthine derivatives were identified as micromolar inhibitors of EphB4 by high-throughput fragment-based docking into the ATP-binding site of the kinase domain. Here, we have exploited the binding mode obtained by automatic docking for the optimization of these EphB4 inhibitors by chemical synthesis. Addition of only two heavy atoms, methyl and hydroxyl groups, to compound 4 has yielded the single-digit nanomolar inhibitor 66, with a remarkable improvement of the ligand efficiency from 0.26 to 0.37 kcal/(mol per non-hydrogen atom). Compound 66 shows very high affinity for a few other tyrosine kinases with threonine as gatekeeper residue (Abl, Lck, and Src). On the other hand, it is selective against kinases with a larger gatekeeper. A 45 ns molecular dynamics (MD) simulation of the complex of EphB4 and compound 66 provides further validation of the binding mode obtained by fragment-based docking. 2009 American Chemical Society.
- Lafleur, Karine,Huang, Danzhi,Zhou, Ting,Caflisch, Amedeo,Nevado, Cristina
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supporting information; experimental part
p. 6433 - 6446
(2010/03/31)
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- Easy preparative scale syntheses of labelled xanthines: Caffeine, theophylline and theobromine
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Several easy preparative scale (0.5-1.5 g) syntheses of deuterium labelled caffeine, theophylline and theobromine are described. Some new selective syntheses of theophylline and theobromine have been developed. Labelled xanthines are of great interest in qualitative or quantitative isotope dilution-mass spectrometry, coupled with gas or liquid chromatography, currently performed in anti-doping and forensic laboratories. Copyright
- Balssa, Frederic,Bonnaire, Yves
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- Use of xanthine derivatives for the treatment of nerve damage following an interruption in blood circulation
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Use of xanthine derivatives for the treatment of nerve damage following an interruption in blood circulation. The invention relates to the use of xanthine derivatives of the formula I STR1 in which R2 is a (C1 -C4)-alkyl group and at least one of the symbols R1 and R3 is a radical of the formula II or III STR2 in which A is CHOH, CO or dioxolane, R4 is a hydrogen atom or a (C1 -C4)-alkyl group and n is 0 to 5, and in which R5 and R6 are hydrogen atoms or (C1 -C4)-alkyl groups or, together with the nitrogen atom to which they are bonded, form a 5- to 7-membered ring, it being possible for one carbon atom to be replaced by an oxygen or nitrogen atom, m is 1 or 2 and the other radical R1 or R3, if appropriate, is a hydrogen atom, a (C1 -C6)-alkyl group or a (C3 -C6)-alkenyl group, for the preparation of medicaments for the prophylaxis and treatment of nerve damage following an interruption in blood circulation, and novel xanthine derivatives, and to processes for their preparation.
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- Process for obtaining 3,7-dialkylxanthines from 3-alkyl-xanthines
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Process for obtaining 3,7-dialkylxanthines from 3-alkyl-xanthines 3,7-Dialkylxanthines are obtained from the corresponding 3-alkylxanthines using an alkylating agent in the presence of quaternary ammonium and/or phosphonium compounds and, where appropriate, of additional polyethers in a two-phase mixture.
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- CATALYTIC HYDROGENATION AND FORMYLATION OF 3-METHYL-4-AMINO-5-NITROSO-2,6-DIOXYPYRIMIDINE OVER PALLADIUM CATALYSTS
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A study has been made of hydrogenation of 3-methyl-4-amino-5-nitroso-2,6-dioxypyrimidine into 3-methyl-4,5-diamino-2,6-dioxypyrimidine and formylation of the latter with formic acid.The optimal reaction conditions have been found, which ensure a yield of 3-methyl-4-amino-5-formylamino-2,6-dioxypyrimidine as high as 96percent.
- Anisimova, N. V.,Toporovskaya, M. A.,Pak, A. M.
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p. 1223 - 1224
(2007/10/02)
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- Process for obtaining almost fluorescence-free xanthines
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Process for obtaining almost fluorescence-free xanthines by precipitation of xanthines which still contain an unsubstituted nitrogen atom in the molecule from aqueous-alkaline solution by means of CO2.
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- Structure-activity relationships in a series of xanthine derivatives with antibronchoconstrictory and bronchodilatory activities
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Thirty-one 1,3,7,8-substituted xanthine derivatives have been synthesized and evaluated for bronchodilator and anti-bronchoconstrictory activities in in vitro tracheal relaxation and in vivo bronchospasm inhibition models. Activity tests have been complemented with phosphodiesterase inhibition and toxicological data. Structure-activity relationships are discussed. Compound 21 (1,3-diisobutyl-8-methylxanthine) has been selected for further pharmacological development because of its good activity profile and favourable therapeutic index, which is 14- and 38-fold greater than that of theophylline and IBMX, respectively.
- Merlos,Gomez,Vericat,Bartroli,Garcia-Rafanell,Forn
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p. 653 - 658
(2007/10/02)
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- Demethylation of N-methylisocyanurate, N-methyluracils and N-methylxanthines by thiophenolate anions
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N-methyls present in the title compounds have been demethylated by sodium thiophenolate at 250-300 deg C under N2 atmosphere.The reaction has been utilised to prepare 1,3-dimethylisocyanuric acid, 1-methyl-6-iminouracil (4) and purine alkaloids 6, 7 and 8 by a new one-step method.
- Mitra, R. B.,Subbarao, A.,Gumaste, V. K.,Likhite, S. M.
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p. 311 - 312
(2007/10/02)
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- Tertiary hydroxyalkylxanthines, medicaments containing them and their use
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Tertiary hydroxyalkylxanthines having the general formula (I), characterized by the fact that at least one of the residues R1 and R3 represents a tertiary hydroxyalkyl group of formula (Ia) in which R4 represents an alkyl group having up to 3 carbon atoms and n a whole number from 2 to 5; the other residue which may remain R1 or R3 is a hydrogen atom or an aliphatic hydrocarbon residue R5 having up to 6 carbon atoms, in which the carbon chain may be separated by a maximum of two oxygen atoms or be substituted by an oxo group or two hydroxy groups at the most, and R2 represents an alkyl group with 1 to 4 carbon atoms. Also described is a process for manufacturing these compounds, which are suitable for the manufacture of medicines, in particular for use in the prevention and/or treatment of peripheral and/or cerebral irrigation disorders. STR1
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- 3-METHYLXANTHOSINE: SYNTHESIS AND ACIDIC HYDROLYSIS OF THE GLYCOSYL BOND
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An improved synthesis of 3,9-dimethylxanthine (2a) was achieved via the reaction of 1-methyl-5-(methylamino)-imidazole-4-carboxamide (3a) with EtOCOCl in acetate buffer (pH 5) followed by treatment with aqueous NaOH.This method was successfully applied to the synthesis of 3-methylxanthosine (2b), whose N-glycosidic bond proved to be remarkably sensitive to acidic hydrolysis: 2b underwent hydrolysis at a rate more than 1000 times faster than that of xanthosine (10) in 1.0N aqueous HCl at 25 deg C.Keywords: 3-methylxanthosine synthesis; 3,9-disubstituted xanthine; imidazolylcarbamic acid ester; base-catalyzed cyclization; amide carbamate cyclization; N-glycosidic bond hydrolysis; carbamate cis-trans isomerism; NMR; kinetic study
- Itaya, Taisuke,Harada, Tsunehiro
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p. 1235 - 1238
(2007/10/02)
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- SYNTHESIS OF 3-METHYLXANTHOSINE
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Treatment of 1-(2,3,5-tri-O-acetyl-β-D-ribofuranosyl)-5-(methylamino)imidazole-4-carboxamide (VIb) with EtOCOCl followed by cyclization with 1 N NaOH gave 3-methylxanthosine (Va).The glycosidic bond of Va underwent acid hydrolysis at a rate more than 1000 times greater than that of xanthosine.
- Itaya, Taisuke,Harada, Tsunehiro
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p. 687 - 690
(2007/10/02)
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- On the mechanism of reactions of oncogenic n-acyloxypurines-III. Extent of radical participation1 1 This investigation was supported in part by Grants Number CA-08748 and CA-23622, awarded by the National Cancer Institute, DHEW. Ref. 20 is now designated as II in the series and Ref. 16 is designated as I.
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UV irradiation of a model "activated ester" of the oncogen 3-hydroxyxanthine induced homolytic cleavage of the N-O bond and gave products arising by reduction of as well as by recombination of the solvent caged amidyl radical intermediate. Identification of the latter product constitutes the first evidence that a distinct product associated specifically with a radical from an acyloxypurine can be formed. The absence of this product among those formed spontaneously from 3-acetoxyxanthine provides the first indication that an amidyl radical is not an intermediate in the spontaneous reactions of N-acyloxy purines.
- Parham, James C.,Templeton, Mary Agnes
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p. 709 - 713
(2007/10/02)
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