- Interrogating the mechanism of a tight binding inhibitor of AIR carboxylase
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The enzyme aminoimidazole ribonucleotide (AIR) carboxylase catalyzes the synthesis of the purine intermediate, 4-carboxy-5-aminoimidazole ribonucleotide (CAIR). Previously, we have shown that the compound 4-nitro-5-aminoimidazole ribonucleotide (NAIR) is
- Firestine, Steven M.,Wu, Weidong,Youn, Hasik,Jo Davisson
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- Solid phase synthesis of nucleobase and ribose modified inosine nucleoside analogues
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The synthesis and the use of new N-1-dinitrophenyl-inosine based solid support is reported. The support, which binds the nucleoside by a 5′-O-monomethoxytrityl function, reacting with N-nucleophiles allowed the synthesis of a small library of N-1 alkylated inosine and AICAR derivatives. Moreover, the obtained supports, after the cleavage of the 2′ -3′ ribose bond, furnished a set of new N-1 alkylated-2′ -3′ -secoinosine derivatives in high yields. Copyright Taylor & Francis Group, LLC.
- Oliviero, Giorgia,Amato, Jussara,D'Errico, Stefano,Borbone, Nicola,Piccialli, Gennaro,Mayol, Luciano
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- Synthesis of N-1 and ribose modified inosine analogues on solid support
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Herein, we report the synthesis and the use of new N-1-dinitrophenyl-inosine based solid supports, in which the C-2 of the purine base is strongly activated toward the attack of N-nucleophiles. The synthesized supports, binding the nucleoside by a 5′-O-monomethoxytrityl function, have been used to accomplish the synthesis of a small library of N-1 alkylated inosine and AICAR derivatives. In addition, cleavage of the 2′-3′ ribose bond of N-1 alkylated inosine derivatives anchored to the supports allowed to prepare a new set of N-1 alkylated-2′,3′-secoinosine derivatives in high yields.
- Oliviero, Giorgia,Amato, Jussara,Borbone, Nicola,D'Errico, Stefano,Piccialli, Gennaro,Mayol, Luciano
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- SAICAR Synthesis method
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A method of synthesizing SAICAR of the present invention is carried out at 5 - amino -1 - ((). 2R. 3R. 4S. 5R-3, 4 -dihydroxy -5 - (hydroxymethyl) tetrahydrofuran -2 -yl) -1H- Imidazol -4 - formamide is the starting material and is sequentially subjected to 5 - amino -1 - ((). 3aR. 4R. 6R. 6aR) -6 - (Hydroxymethyl) -2, 2 -dimethyltetrahydrofuran [3,4 -]d] [1, 3] Diox -4 - group) -1H-imidazole -4 -carboxamide. 5 - Amino -1 - (()3aR. 4R. 6R. 6aR) -6 - (Hydroxymethyl) -2, 2 -dimethyltetrahydrofuran [3,4 -]d] [1, 3] Diox -4 - group) -1H- Imidazole -4 - carboxylic acid, dibenzyl (5 - amino -1 -) (()3aR. 4R. 6R. 6aR) -6 - (Hydroxymethyl) -2, 2 -dimethyltetrahydrofuran [3,4 -]d] [1, 3] Diox -4 - group) -1H- Imidazol -4 - carbonyl) . LOf - aspartic acid and the like to obtain a finished product purity of up to 99.6%, impurities 0.4%, diastereomeric excess (de) values 97.3% and a yield 16.9%.
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- IMPROVEMENTS TO ANALOGOUS COMPOUNDS OF 6-THIOGUANOSINE TRIPHOSPHATE, THEIR USE IN MEDICAL FIELDS AND PROCESSES FOR THEIR PREPARATION
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The invention relates to analogous compounds of 6-thioguanosine triphosphate of general formula (I). A compound of the general formula (I); wherein the dashed bond in the sugar moiety can be either single or double and wherein R1 , R2, R3, R4 or R5, equal or different between each other, have general formula -(Int)m-Ter, wherein m is between 0 and 12 and lnt and Ter are Internal and Terminal building blocks, wherein lnt is selected from the group consisting of formula (II); and Ter is selected from the group consisting of formula (III). And wherein X represents either carbon or nitrogen atom within aromatic ring, Y represents either oxygen or sulphur atom and an additional group Q, group Qi or groups Qi (Qi indicates that the group or several groups may be bound to any unsaturated moiety of the ring) are selected from the group consisting of -OH, -COOH, -N(CH3)2, -N(CH2-CH3)2| -CO-CH3, -CO-O-CH3, -O-CH3, -S-CH3,-SO2-CH3, -CN, -NO2 or -Halogen elements, and wherein R5 may be formula (IV) and metal and ammonium salts thereof, wherein n is between O and 5, or oxygen or phosphorus is partially or completely replaced by nitrogen, sulphur, methyleno groups or their derivatives. The invention also concerns the uses of the above mentioned compounds in medical field and the process for their preparation.
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Page/Page column 65
(2008/06/13)
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- A Facile Synthesis of AICAR from Inosine
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5-Amino-1-β-D-ribofuranosylimidazole-4-carboxamide (AICAR; 1) (Figure 1) was efficiently prepared from inosine through its 1-alkoxymethylderivatives. The stability of these derivatives enabled their purification by column chromatography (silica gel). The operation ensured the high quality of 1, which was obtained in good yield through alkaline hydrolysis of the derivatives.
- Kohyama, Naoki,Yamamoto, Yukio
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p. 2639 - 2642
(2007/10/03)
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- Purines. LXIV syntheses of 9-methyl-2-azaadenine 1-oxide, its O-methyl derivative, and 1-substituted 5-azidoimidazole-4-carboxamides
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Diazotization of 5-amino-N'-methoxy-1-methylimidazole-4-carboxamidine (4a) with NaNO2, in 1 N aqueous HCl was found to give the 1-methoxy-2-azaadenine derivative 8a · HI, which produced 5-azido-1-methylimidazole-4-carbonitrile (5a) on treatment with aqueous Na2CO3. The ribosyl analogue 5b, obtained from the riboside 4b by similar diazotization, was utilized for the synthesis of 5-azido-1-β-D-ribofuranosylimidazole-4-carboxamide (9b), a novel AICA riboside analogue. On heating in HCONMe2 at 700C for 10 min, 8a · HI yielded the 1-N-oxide 7a. Several reactions to transform the functional groups in 5a were also investigated.
- Saito,Asahi,Nakajima,Fujii
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p. 2263 - 2268
(2007/10/02)
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- A UNIQUE TRANSFORMATION OF 5-AMINO-N'-METHOXYIMIDAZOLE-4-CARBOXAMIDINES BY DIAZOTIZATION: SYNTHESIS OF THE 5-AZIDO ANALOGUE OF AICA RIBOSIDE
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Diazotization of 1-substituted 5-amino-N'-methoxyimidazole-4-carboxamidines (I) was found to give the 5-azidoimidazole-4-carbonitriles II through the 1-methoxy-2-azaadenine intermediates IV.The product IIb from the riboside Ib was utilized for the synthesis of 5-azido-1-β-D-ribofuranosylimidazole-4-carboxamide (Vb), a novel AICA riboside analogue.
- Saito, Tohru,Asahi, Yayoi,Nakajima, Satoshi,Fujii, Tozo
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p. 329 - 332
(2007/10/02)
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- Nucleosides from Carbohydrate Adducts of Diaminomaleonitrile. A Novel Synthesis of 5-Amino-1-(β-D-ribofuranosyl)imidazole-4-carboxamide and 5-Amino-1-(β-D-ribopyranosyl)imidazole-4-carboxamide
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The stereospecific and regiospecific synthesis of 5-amino-1-(β-D-ribofuranosyl)imidazole-4-carboxamide (16) was achieved in six steps.A key intermediate in the synthesis, N-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)diaminomaleonitrile (3), was prepared by two routes: the reaction of diaminomaleonitrile (1) with 1-bromo-2,3,5-tri-O-benzoyl-β-D-ribofuranose (2) and the reaction of the bis(trimethylsilyl) derivative of diaminomaleonitrile (4) with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose (5).Reaction of 3 triethyl orthoformate yielded 4,5-dicyano-1-(2',3',5'-tri-O-benzoyl-β-D-ribofuranosyl)imidazole (10).Alternatively 10 was synthesized by the acid-catalyzed cyclization of the N-formyl derivative 12 which was prepared by the reaction of the trimethylsilyl derivative of N-formyldiaminomaleonitrile 11 with 5.Deblocking 10 with 1 equiv of sodium methoxide at room temperature resulted in the regiospecific formation of the 5-imidate 14.Reaction of 14 with alkaline hypochlorite yielded 5-amino-1-(β-D-ribofuranosyl)imidazole-4-carbonitrile (15) by a Hofmann rearrangement.Alkaline hydrolysis of the nitrile function yielded the corresponding amide 16. 5-Amino-1-(β-D-ribopyranosyl)imidazole-4-carboxamide (28) was prepared by a similar synthetic sequence.Reaction of diaminomaleonitrile (1) with ribose gave a mixture of the α- and β-anomers of D-ribopyranosyldiaminomaleonitrile (17).Compound 17 was converted to a mixture of the anomeric tri-O-acetates which on heating with triethyl orthoformate gave a separable mixture of the α- and β-anomers of 4,5-dicyano-1-(2',3',4'-tri-O-acetyl-D-ribopyranosyl)imidazole (19 and 20, respectively).Reaction of 19 with NH3/CH3OH at room temperature cleaved the three acetyl groups and regiospecifically converted the 5-cyano to the 5-imidate (26).The regiospecificity is due to the attack of the 2'-oxy anion on the 5-cyano group as shown by the isolation of the cyclic imidate 25 when the reaction is carried out at 0 deg C.The Hofmann rearrangement of imidate 26 followed by alkaline hydrolysis gave 5-amino-1-(β-D-ribopyranosyl)imidazole-4-carbonitrile 27 and 28, respectively.The 1H and 13C NMR spectra of imidates 14 and 26 have multiple peaks for the protons and carbons, respectively.Restricted rotation of the 5-imidate (energy of activation 18 kcal) results in isomers of 14 and 26 with different NMR spectra.The C-2, H-1' coupling constants of 2.5-3.1 Hz of the isomeric species comprising imidates 14 and 26 are consistent with a H-2, H-1' dihedral angle of 135 deg and an anti orientation of the imidazole with respect to the ribose ring; a conclusion confirmed by NOE measurements.
- Ferris, James P.,Devadas, Balekadru,Huang, Chun-Hsien,Ren, Wu-Yen
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p. 747 - 754
(2007/10/02)
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