- Fluorescing Isofunctional Ribonucleosides: Assessing Adenosine Deaminase Activity and Inhibition
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The enzymatic conversion of isothiazolo[4,3-d]pyrimidine-based adenosine (tzA) and 2-aminoadenosine (tz2-AA) analogues to the corresponding isothiazolo[4,3-d]pyrimidine-based inosine (tzI) and guanosine (tzG) derivatives is evaluated and compared to the conversion of native adenosine to inosine. Henri–Michaelis–Menten analyses provides the foundation for a high-throughput screening assay, and the efficacy of the assay is showcased by fluorescence-based analysis of tzA conversion to tzI in the presence of known and newly synthesized inhibitors.
- Ludford, Paul T.,Rovira, Alexander R.,Fin, Andrea,Tor, Yitzhak
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p. 718 - 726
(2019/03/05)
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- 5. 7 - Dichloro - 1 H - imidazo [4, 5 - B] pyridine synthesis method
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The invention discloses a method for synthesizing 5,7-dichloro-1H-imidazo-[4,5-B] pyridine. The method comprises steps as follows: in the presence of ammonium chloride, ethyl acetate and water, a compound 1 is reduced by iron powder to obtain a compound 2; the compound 2 has a reflux reaction with p-toluenesulfonic acid monohydrate and triethyl orthoformate to obtain a compound 3; acetic acid is taken as a solvent, the compound 3 reacts with m-chloroperoxybenzoic acid to a compound 4; the compound 4 has a reflux reaction with phosphorus oxychloride at the temperature of 0-5 DEG C in the presence of DMF (Dimethyl formamide) so as to obtain 5,7-dichloro-1H-imidazo-[4,5-B] pyridine. A brand-new synthesis path of 5,7-dichloro-1H-imidazo-[4,5-B] pyridine is provided, raw materials are easy to obtain, the preparation process is simple, the yield is high, the cost is low, and large-scale production can be realized.
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Paragraph 0050-0052
(2017/12/06)
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- IMIDAZOPYRIDINE DERIVATIVES AS PI3 KINASE INHIBITORS
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This invention relates to the use of imidizopyridine derivatives for the modulation, notably the inhibition of the activity or function of the phosphoinositide 3' OH kinase family (hereinafter PI3 kinases), suitably, PI3Kα, PI3Kδ, PI3Kβ, and/or PI3Kγ. Suitably, the present invention relates to the use of imidizopyridines in the treatment of one or more disease states selected from: autoimmune disorders, inflammatory diseases, cardiovascular diseases, neurodegenerative diseases, allergy, asthma, pancreatitis, multiorgan failure, kidney diseases, platelet aggregation, cancer, sperm motility, transplantation rejection, graft rejection and lung injuries. More suitably, the present invention relates to PI3Kβ selective imidizopyridine compounds for treating cancer.
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Page/Page column 32; 33; 34
(2013/07/05)
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- 2,6,8-Trisubstituted 1-deazapurines as adenosine receptor antagonists
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In this study we developed a refined pharmacophore model for antagonists of the human adenosine A1 receptor, based on features of known pyrimidine and purine derivatives. The adoption of these updated criteria assisted us in synthesizing a series of 1-deazapurines with consistently high affinity as inverse agonists for the adenosine A1 receptor. These 1-deazapurines (otherwise known as 3H-imidazo[4,5-b]pyridines) were substituted at their 2- and 6-positions, yielding a series with five of the derivatives displaying Ki values in the subnanomolar range. The most potent of these, compound 10 (LUF 5978), displayed an affinity of 0.55 nM at the human adenosine A1 receptor with > 300-fold and 45-fold selectivity toward A2A and A3 receptors, respectively. Compound 14 (LUF 5981, Ki = 0.90 nM) appeared to have the best overall selectivity with respect to adenosine A2A (> 200-fold) and A 3 (700-fold) receptors.
- Chang, Lisa C. W.,Von Frijtag Drabbe Künzel, Jacobien K.,Mulder-Krieger, Thea,Westerhout, Joost,Spangenberg, Thomas,Brussee, Johannes,Ijzerman, Adriaan P.
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p. 828 - 834
(2007/10/03)
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- Inhibition of nucleoside transport by new analogues of nitrobenzylthioinosine
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Nitrobenzylthioinosine (NBTI, 1) was systematically modified by attachment of substituents at positions C6 and N9, and also by substitution of N1 with C. These modifications were chosen to reduce the polarity of the new compounds. Incorporation of the nitro functionality into a benzoxadiazole ring system was considered first. These new nucleosides showed high affinity (1.5-10 nM) towards the nucleoside transport protein as present on human erythrocyte ghosts. Next, modification of this benzoxadiazole ring system with C, S and O in different positions produced a number of less polar nucleosides with affinity in the higher nanomolar range. Modification of N9 was achieved with different alkyl and alcohol substituents. An n-butyl substituent proved best, although all variations yielded substantial decreases in affinity. Replacement of N1 by a carbon atom in combination with a 2-Cl substituent also resulted in a relatively potent NBTI derivative (47 nM).
- Deghati, Paymaneh Y. F.,Borghini, Alice,Van Den Nieuwendijk, Adrianus M. C. H.,Dissen-de Groote, Miriam,IJzerman, Adriaan P.
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p. 899 - 908
(2007/10/03)
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- New analogs of nitrobenzylthioinosine
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This invention relates to new analogs or derivatives of nitrobenzylthioinosine, use of these new analogs of nitrobenzylthioinosine for the treatment of pain and various other diseases as well as pharmaceuticals comprising at least on new analog of nitrobenzylthioinosine.
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Page/Page column 32-33
(2010/11/29)
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- F-substituted-3-β-D-ribofuranosyl-3H-imidazo[4,5-b]pyridines and pharmaceutical compositions thereof
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This invention discloses a group of compounds of formula (I) STR1 wherein R1 is hydrogen, halo, C1-4 alkyl, C1-4 alkoxy, COOR4 (R4 is H or C1-4 alkyl) or trifluoromethyl; R2, R5 and R6 are the same or different and can be hydrogen, hydroxy, OCOR7 (wherein R7 is hydrogen, C1-4 alkyl, phenyl optionally substituted) or halo; and R3 is hydrogen, COR4, C3-6 cycloalkyl or C1-4 alkyl or alkenyl; R2 may also be a phosphate group and pharmaceutically acceptable salts thereof which have been found to have analgesic activity. In addition, these compounds have antiinflammatory, antipyretic, antihypertensive and vasodilatory activity in varying degrees. Some of these compounds also have antiprotozoal and antiviral properties.
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