7013-16-3

Usage

Uses

Used in Pharmaceutical Industry:
HYPOXANTHINE-9-BETA-D-ARABINOFURANOSIDE is used as an intermediate compound for the synthesis of various antiviral and anticancer drugs. Its unique chemical structure makes it a valuable building block in the development of new pharmaceuticals with improved efficacy and reduced side effects.
Used in Antiviral Drug Development:
HYPOXANTHINE-9-BETA-D-ARABINOFURANOSIDE is used as a key component in the preparation of 5''-O-D-valyl adenine 9-β-D-arabinofuranoside, a potential prodrug for improving the oral bioavailability of the antiviral agent Vidarabine (V305030). This application aims to enhance the effectiveness of Vidarabine in treating viral infections by increasing its bioavailability and reducing the need for frequent injections.

InChI:InChI=1/C10H12N4O5/c15-1-4-6(16)7(17)10(19-4)14-3-13-5-8(14)11-2-12-9(5)18/h2-4,6-7,10,15-17H,1H2,(H,11,12,18)/t4-,6-,7+,10-/m1/s1

Upstream product

• 5536-17-4 arabinosyl adenine 
• 52522-49-3 2,3,5-tri-O-benzyl-1-(4-nitrobenzoyloxy)-D-arabinofuranose 
• 4060-34-8 2,3,5-tri-O-benzyl-α-D-arabinofuranosyl chloride 
• 37776-25-3 2,3,5-tri-O-benzyl-D-arabinose 
• 108321-99-9 α,β-D-arabinofuranose-5-phosphate disodium salt 
• 68-94-0 hypoxanthine 
• 38819-10-2 9-β-D-arabinofuranosylguanine 
• 73-40-5 2-amino-1,9-dihydro-6H-purin-6-one 
• 3083-77-0 araU 
• 68-94-0 Allopurinol 
• 58-63-9 inosine 
• 69275-14-5 ethyl 5-amino-1-(2,3,5-tri-O-benzyl-β-D-arabinofuranosyl)imidazole-4-carboxylate 

Downstream Products

• 5987-73-5 (2R,3R,4S,5R)-2-(acetoxymethyl)-5-(6-chloro-9H-purin-9-yl)tetrahydrofuran-3,4-diyl diacetate 
• 110505-76-5 6-(3-hydroxybenzylamino)-9-β-D-arabinofuranosylpurine 
• 1187-84-4 S-methyl-L-cysteine 
• 2140-73-0 1-methylinosine 
• 31504-19-5 1-benzylinosine 
• 99051-98-6 1-benzyl-6-oxo-9-<(2R,6R)-6-hydroxymethyl-1-oxa-4-thiacyclohexan-2-yl>-9H-purine 
• 99236-82-5 1-benzyl-6-oxo-9-<(2R,6R)-6-tertbutyldimethylsilyloxymethyl-1-oxa-4-thiacyclohexane-2-yl>-9H-purine 
• 99236-78-9 1-benzyl-5'-O-tert-butyldimethysilylinosine 
• 99236-80-3 1-Benzyl-9-{(S)-1-[(R)-2-(tert-butyl-dimethyl-silanyloxy)-1-hydroxymethyl-ethoxy]-2-hydroxy-ethyl}-1,9-dihydro-purin-6-one 
• 99236-81-4 Toluene-4-sulfonic acid (R)-2-(1-benzyl-6-oxo-1,6-dihydro-purin-9-yl)-2-[(S)-2-(tert-butyl-dimethyl-silanyloxy)-1-hydroxymethyl-ethoxy]-ethyl ester 
• 68-94-0 Allopurinol 
• 72075-46-8 O¹-Phosphono-α-D-arabinofuranose 

Relevant academic research and scientific papers

5′-O-D-valyl ara A, a potential prodrug for improving oral bioavailability of the antiviral agent vidarabine

In order to improve the oral bioavailability of Adenine 9-β-D-arabinofuranoside (Vidarabine, also called ara A), an antiviral drug which is active against herpes simplex and varicella zoster viruses and the first agent to be licensed for the treatment of

Enzymatic Synthesis of Therapeutic Nucleosides using a Highly Versatile Purine Nucleoside 2’-DeoxyribosylTransferase from Trypanosoma brucei

The use of enzymes for the synthesis of nucleoside analogues offers several advantages over multistep chemical methods, including chemo-, regio- and stereoselectivity as well as milder reaction conditions. Herein, the production, characterization and utilization of a purine nucleoside 2’-deoxyribosyltransferase (PDT) from Trypanosoma brucei are reported. TbPDT is a dimer which displays not only excellent activity and stability over a broad range of temperatures (50–70 °C), pH (4–7) and ionic strength (0–500 mM NaCl) but also an unusual high stability under alkaline conditions (pH 8–10). TbPDT is shown to be proficient in the biosynthesis of numerous therapeutic nucleosides, including didanosine, vidarabine, cladribine, fludarabine and nelarabine. The structure-guided replacement of Val11 with either Ala or Ser resulted in variants with 2.8-fold greater activity. TbPDT was also covalently immobilized on glutaraldehyde-activated magnetic microspheres. MTbPDT3 was selected as the best derivative (4200 IU/g, activity recovery of 22 %), and could be easily recaptured and recycled for >25 reactions with negligible loss of activity. Finally, MTbPDT3 was successfully employed in the expedient synthesis of several nucleoside analogues. Taken together, our results support the notion that TbPDT has good potential as an industrial biocatalyst for the synthesis of a wide range of therapeutic nucleosides through an efficient and environmentally friendly methodology.

The arsenolysis reaction in the biotechnological method of synthesis of modified purine β-D-arabinonucleosides

We found a unique property of E. coli purine nucleoside phosphorylases to selectively perform the arsenolysis reaction of ribonucleosides in their active site without affecting β-D-arabinonucleosides. In the synthesis of modified β-D-arabinonucleosides from the corresponding ribonucleosides, the catalytical amount of sodium arsenate in the transglycosylation reaction provided a 95 to 98% conversion rate. Such an approach was shown to simplify the composition of the reaction mixtures and facilitate the isolation of the target nucleosides, particularly, vidarabine, fludarabine, and nelarabine.

Chemoenzymatic preparation of nucleosides from furanoses

Chemoenzymatic preparation of ribose, deoxyribose and arabinose 5-phosphates was accomplished. These compounds were tested as starting materials in the enzymatic preparation of natural and modified purine and pyrimidine nucleosides, using an overexpressed Escherichia coli phosphopentomutase.

Nucleoside derivatives as inhibitors of RNA-dependent RNA viral polymerase

The present invention provides nucleoside compounds and certain derivatives thereof which are inhibitors of RNA-dependent RNA viral polymerase. These compounds are inhibitors of RNA-dependent RNA viral replication and are useful for the treatment of RNA-dependent RNA viral infection. They are particularly useful as inhibitors of hepatitis C virus (HCV) NS5B polymerase, as inhibitors of HCV replication, and/or for the treatment of hepatitis C infection. The invention also describes pharmaceutical compositions containing such nucleoside compounds alone or in combination with other agents active against RNA-dependent RNA viral infection, in particular HCV infection. Also disclosed are methods of inhibiting RNA-dependent RNA polymerase, inhibiting RNA-dependent RNA viral replication, and/or treating RNA-dependent RNA viral infection with the nucleoside compounds of the present invention.

Prodrug azide compositions and compounds

Pharmaceutical prodrug compositions are provided comprising azide derivatives of drugs which are capable of being converted to the drug in vivo. Azide derivatives of drugs having amine, ketone and hydroxy substituents are converted in vivo to the corresponding drugs, increasing the half-life of the drugs. In addition azide prodrugs are often better able to penetrate the blood-brain barrier than the corresponding drugs. Especially useful are azide derivatives of cordycepin, 2′-F-ara-ddI, AraA, acyclovir, penciclovir and related drugs. Useful azide prodrugs are azide derivatives of therapeutic alicyclic amines, ketones, and hydroxy-substituted compounds, including aralkyl, heterocyclic aralkyl, and cyclic aliphatic compounds, where the amine or oxygen moiety is on the ring, or where the amine or oxygen moiety is on an aliphatic side chain, as well as therapeutic purines and pyrimidines, nucleoside analogs and phosphorylated nucleoside analogs.

Synthesis, biotransformation, and pharmacokinetic studies of 9-(β-D- arabinofuranosyl)-6-azidopurine: A prodrug for ara-A designed to utilize the azide reduction pathway

As a part of our efforts to design prodrugs for antiviral nucleosides, 9-(β-D-arabinofuranosyl)-6-azidopurine (6-AAP) was synthesized as a prodrug for ara-A that utilizes the azide reduction biotransformation pathway. 6-AAP was synthesized from ara-A via its 6-chloro analogue 4. The bioconversion of the prodrug was investigated in vitro and in vivo, and the pharmacokinetic parameters were determined. For in vitro studies, 6-AAP was incubated in mouse serum and liver and brain homogenates. The half-lives of 6-AAP in serum and liver and brain homogenates were 3.73, 4.90, and 7.29 h, respectively. 6- AAP was metabolized primarily in the liver homogenate microsomal fraction by the reduction of the azido moiety to the amine, yielding ara-A. However, 6- AAP was found to be stable to adenosine deaminase in a separate in vitro study. The in vivo metabolism and disposition of ara-A and 6-AAP were conducted in mice. When 6-AAP was administered by either oral or intravenous route, the half-life of ara-A was 7-14 times higher than for ara-A administered intravenously. Ara-A could not be found in the brain after the intravenous administration of ara-A. However, after 6-AAP administration (by either oral or intravenous route), significant levels of ara-A were found in the brain. The results of this study demonstrate that 6-AAP is converted to ara-A, potentially increasing the half-life and the brain delivery of ara-A. Further studies to utilize the azide reduction approach on other clinically useful agents containing an amino group are in progress in our laboratories.

Purines, Pyrimidines, and Imidazoles. Part 52. New Syntheses of Some 1-β-D-Arabinofuranosylaminoimidazoles and of Related Purine Nucleosides, including 9-β-D-Arabinofuranosyladenine

Ethyl 5-amino-1-β-D-arabinofuranosylimidazole-4-carboxylate and the corresponding carboxamide have been prepared by reaction of ethyl 5-aminoimidazole-4-carboxylate or the carboxamide, respectively with 2,3,5-tri-O-benzyl-α-D-arabinofuranosyl chloride (but not the bromide or iodide) and deblocking.Reaction of the nucleoside ester with formamidine acetate gave 9-β-D-arabinofuranosylhypoxanthine. 5-Amino-4-cyano-1-β-D-arabinofuranosylimidazole obtained by dehydration of the benzylated carboxamide or by direct glycosylation of 5-amino-4-cyanoimidazole and debenzylation of the product, when heated with triethyl orthoformate and ammonia, gave 9-β-D-arabinofuranosyladenine. 2,3,5-Tri-O-benzylarabinofuranosyl chloride with sodium azide, followed by reduction of the glycosyl azide formed with platinic oxide, and condensation of the arabinosylamine produced with ethyl N-(carbamoylcyanomethyl)formimidate gave a mixture of 2,3,5-tri-O-benzyl 1-α- and -β-D-arabinofuranosylimidazole 4-carboxamides.Reduction of the azide with lithium aluminium hydride followed by debenzylation of the product gave, in addition to tho two anomers, 5-amino-1-D-arabinitylimidazole-4-carboxamide.