- HYDROXYL PURINE COMPOUNDS AND USE THEREOF
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Disclosed are a series of hydroxyl purine compounds and the use thereof as PDE2 or TNFα inhibitors, in particular, the compounds as shown in formula (I), or tautomers thereof or pharmaceutically acceptable salts thereof.
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Paragraph 0433; 0434; 0435
(2018/04/05)
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- Fragment Discovery for the Design of Nitrogen Heterocycles as Mycobacterium tuberculosis Dihydrofolate Reductase Inhibitors
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Fragment-based drug design was used to identify Mycobacterium tuberculosis (Mtb) dihydrofolate reductase (DHFR) inhibitors. Screening of ligands against the Mtb DHFR enzyme resulted in the identification of multiple fragment hits with IC50 values in the range of 38–90 μM versus Mtb DHFR and minimum inhibitory concentration (MIC) values in the range of 31.5–125 μg/mL. These fragment scaffolds would be useful for anti-tubercular drug design.
- Shelke, Rupesh U.,Degani, Mariam S.,Raju, Archana,Ray, Mukti Kanta,Rajan, Mysore G. R.
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p. 602 - 613
(2016/08/28)
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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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experimental part
p. 476 - 482
(2011/04/22)
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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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- Therapeutic compounds for inhibiting interleukin-12 signals and method for using same
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Novel heterocyclic compounds having a six membered ring structure fused to a five membered ring structure are found to be useful for the treatment and prevention of symptoms or manifestations associated with disorders affected by Interleukin-12 (“IL-12”) intracellular signaling, such as, for example, Th1 cell-mediated disorders. The therapeutic compounds, pharmaceutically acceptable derivatives (e.g., resolved enantiomers, diastereomers, tautomers, salts and solvates thereof) or prodrugs thereof, have the following general formula: Each X, Y and Z are independently selected from a member of the group consisting of C(R3), N, N(R3) and S. Each R1, R2 and R3 is substituted or unsubstituted and is independently selected from a member of the group consisting of hydrogen, halo, oxo, C(1-20)alkyl, C(1-20)hydroxyalkyl, C(1-20)thioalkyl, C(1-20)alkylamino, C(1-20)alkylaminoalkyl, C(1-20)aminoalkyl, C(1-20)aminoalkoxyalkenyl, C(1-20)aminoalkoxyalkynyl, C(1-20)diaminoalkyl, C(1-20)triaminoalkyl, C(1-20)tetraaminoalkyl, C(5-15)aminotrialkoxyamino, C(1-20)alkylamido, C(1-20)alkylamidoalkyl, C(1-20)amidoalkyl, C(1-20)acetamidoalkyl, C(1-20)alkenyl, C(1-20)alkynyl, C(3-8)alkoxyl, C(1-11)alkoxyalkyl, and C(1-20)dialkoxyalkyl.
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- COMBINATION DRUG
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The present invention provides pharmaceutical agents comprising a dipeptidyl peptidase IV (DPPIV) inhibitor and a biguanide agent in combination, which enhance the effects of active circulating glucagon-like peptide-1 (GLP-1) and/or active circulating glucagon-like peptide-2 (GLP-2).
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Page/Page column 101
(2010/02/12)
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- Therapeutic compounds for inhibiting interleukin-12 signaling and methods for using same
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Novel heterocyclic compounds having a six membered ring structure fused to a five membered ring structure are found to be useful for the treatment and prevention of symptoms or manifestations associated with disorders affected by Interleukin-12 (“IL-12”) intracellular signaling, such as, for example, Th1 cell-mediated disorders. The therapeutic compounds, pharmaceutically acceptable derivatives (e.g., resolved enantiomers, diastereomers, tautomers, salts and solvates thereof) or prodrugs thereof, have the following general formula: Each X, Y and Z are independently selected from a member of the group consisting of C(R3), N, N(R3) and S. Each R1, R2 and R3 is substituted or unsubstituted and is independently selected from a member of the group consisting of hydrogen, halo, oxo, C(1-20)alkyl, C(1-20)hydroxyalkyl, C(1-20)thioalkyl, C(1-20)alkylamino, C(1-20)alkylaminoalkyl, C(1-20)aminoalkyl, C(1-20)aminoalkoxyalkenyl, C(1-20)aminoalkoxyalkynyl, C(1-20)diaminoalkyl, C(1-20)triaminoalkyl, C(1-20)tetraaminoalkyl, C(5-15)aminotrialkoxyamino, C(1-20)alkylamido, C(1-20)alkylamidoalkyl, C(1-20)amidoalkyl, C(1-20)acetamidoalkyl, C(1-20)alkenyl, C(1-20)alkynyl, C(3-8)alkoxyl, C(1-11)alkoxyalkyl, and C(1-20)dialkoxyalkyl.
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- Xanthine derivatives as DPP-IV inhibitors
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The present invention provides novel compounds exhibiting an excellent DPPIV inhibition effect. The compounds are represented by the formula: wherein, m is 0 or 1; n is 0; R31, R32, R33, R34, R35, R36, R37, R38, R39, R40, R41, and R42 each represent a hydrogen atom; X represents an alkynyl group, an aryl group, and such, which group may be substituted; and, R1 and R2 each independently represents a hydrogen atom, an alkyl group, an alkoxyl group, or such, or salts or hydrates thereof.
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- THERAPEUTIC COMPOUNDS FOR INHIBITING INTERLEUKIN-12 SIGNALING AND METHODS FOR USING SAME
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Novel heterocyclic compounds having a six membered ring structure fused to a five membered ring structure are found to be useful for the treatment and prevention of symptoms or manifestations associated with disorders affected by Interleukin-12 (“IL-12”) intracellular signaling, such as, for example, Th1 cell-mediated disorders. The therapeutic compounds, pharmaceutically acceptable derivatives (e.g., resolved enantiomers, diastereomers, tautomers, salts and solvates thereof) or prodrugs thereof, have the following general formula: Each X, Y and Z are independently selected from a member of the group consisting of C(R3), N, N(R3) and S. Each R1, R2 and R3 is substituted or unsubstituted and is independently selected from a member of the group consisting of hydrogen, halo, oxo, C(1-20)alkyl, C(1-20)hydroxyalkyl, C(1-20)thioalkyl, C(1-20)alkylamino, C(1-20)alkylaminoalkyl, C(1-20)aminoalkyl, C(1-20)aminoalkoxyalkenyl, C(1-20)aminoalkoxyalkynyl, C(1-20)diaminoalkyl, C(1-20)triaminoalkyl, C(1-20)tetraaminoalkyl, C(5-15)aminotrialkoxyamino, C(1-20)alkylamido, C(1-20)alkylamidoalkyl, C(1-20)amidoalkyl, C(1-20)acetamidoalkyl, C(1-20)alkenyl, C(1-20)alkynyl, C(3-8)alkoxyl, C(1-11)alkoxyalkyl, and C(1-20)dialkoxyalkyl.
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- TRICYCLIC FUSED XANTHINE COMPOUNDS AND THEIR USES
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Novel tricyclic compounds are found to be useful for the treatment or prevention of symptoms or manifestations associated with diseases or disorders affected by cytokine intracellular signaling.
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- Alkylxanthine phosphonates and alkylxanthine phosphine oxides and their use as pharmaceuticals
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Alkylxanthine phosphonates and alkylxanthine phosphine oxides and their use as pharmaceuticals A compound of the formula STR1 where R1 and R3 are identical or different and at least one of the radicals R1 and R3 is a radical of the formula XI STR2 in which E is a covalent bond or a (C1 -C5)-alkyl, are suitable for the production of pharmaceuticals for the treatment of muscular atrophy, cachexia, muscular dystrophy, sepsis, septic shock, endotoxic shock, systemic inflammation response syndrome, adult respiratory distress syndrome, cerebral malaria, chronic pneumonia, pulmonary sarcoidosis, reperfusion damage, scar formation, inflammation of the bowel and ulcerative colitis, as a result of infections, acquired immune deficiency syndrome, cancer, trauma and other disorders having increased protein loss, peripheral circulatory disorders, disorders having altered leucocyte adhesion, and also disorders which are accompanied by an increased or unregulated tumor necrosis factor production such as rheumatoid arthritis, rheumatoid spondylitis, osteoarthritis and other arthritic disorders.
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- SYNTHESIS OF GUANINE FROM 3-METHYLXANTHINE
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A new preparative method of obtaining guanine from 3-methylxanthine has been developed.
- Kochergin, P. M.,Persanova, L. V.,Aleksandrova, E. V.,Gutorov, L. A.,Korsunskii, V. S.
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p. 337 - 339
(2007/10/03)
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- Purines. XLIX. Synthesis and proton nuclear magnetic resonance study of 3,7-dialkylxanthines and 1,3,7-trialkylxanthines
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A general synthetic route to 3,7-dialkylxanthines (type 9) from 3,7-dialkyladenines (6) [hence from 3- or 7-alkyladenines (11 or 10)] has been established. The route started with ethoxycarbonylation of 1-alkyl-4-(alkylamino)1H-imidazole-5-carboxamides (7), readily obtainable from 6 by alkaline hydrolysis, and proceeded through cyclization of the resulting carbamates (8) under alkaline conditions. Alkylation of 9 with alkyl halide in N,N-dimethylformamide in the presence of anhydrous K2CO3 extended the above synthetic route to the 1,3,7-trialkylxanthine level (type 14). Hydrogenolytic deb nzylation of 3-benzyl-1,7-dimethylxanthine (16), prepared by following this general synthetic route, furnished paraxanthine (26) in fair yield. Conversion of 26 into 3-(4-hydroxy-3-nitrobenzyl)-1,7-dimethylxanthine (24), isomeric with the bryozoan purine phidolopin (2), was effected through aralkylation with 4-(methoxymethoxy)-3-nitrobenzyl bromide (28) followed by O-deprotection. On the basis of proton nuclear magnetic resonance data for the 3,7-dialkylxanthines (3 and 9b-i) and 1,3,7-trialkylxanthines (5 and 14-22) thus prepared, reliable criteria for distinguishing signals of N-alkyl substituents at various positions are put forward.
- Fujii,Saito,Tamura
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p. 2855 - 2862
(2007/10/02)
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- Studies towards the synthesis of the fluorescent bases of phenylalanine transfer ribonucleic acids: synthesis of 7-methylwye isolated from extremely thermophilic archaebacteria.
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Acid- or base-catalyzed acylation of 1-benzylwye (7) provided the 7-substituted derivatives 9, 10, and 11 in poor yields. Although the reactions of lithiated 7 with electrophiles gave the 2-substituted derivatives 14, 15, 17, 20, 21, and 22, lithiation of
- Itaya,Mizutani,Takeda,Shioyama
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p. 284 - 291
(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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