20535-04-0

Upstream product

• 58-61-7 adenosine 
• 4099-81-4 5'-iodo-5'-deoxyadenosine 
• 79849-81-3 Desoxy-5'o-nitrophenylselenoxy-5'adenosine 
• 79849-80-2 Desoxy-5'-o-nitrophenylselenyl-5'adenosine 

Downstream Products

• 157031-43-1 2',3',N,N-tetrabenzoyl-4',5'-didehydro-5'-deoxyadenosine 
• 68200-73-7 6-N-benzoyl-9-(5-deoxy-β-D-erythro-pent-4-enofuranosyl)adenine 

Relevant academic research and scientific papers

First example of phosphoramidate approach applied to a 4′-substituted purine nucleoside (4′-Azidoadenosine): Conversion of an inactive nucleoside to a submicromolar compound versus hepatitis C virus

We report on the synthesis of the anti hepatitis C virus (HCV) agent 4′-azidoadenosine (1) and the application of the phosphoramidate ProTide technology to this nucleoside. The synthesis of 1 was achieved through an epoxide intermediate followed by regio- and stereoselective ring opening by azidotrimethylsilane in the presence of a Lewis acid. Compound 1 did not inhibit HCV replication in cell culture at concentrations up to 0.1 mM. However, a submicromolar active agent could be derived from 1 by the application of the ProTide technology. All the phosphoramidates prepared were L-alanine derivatives with variations in the aryl moiety and in the ester part of the amino acid. The benzyl ester and the 1-naphthyl phosphate (18) had the best activity in replicon assay. Phosphoramidates (18-21) achieved a significant improvement in antiviral potency over the parent nucleoside (1) with no increase in cytotoxicity.

5′-Phosphonate modified oligoadenylates as potent activators of human RNase L

The oligoadenylate synthetase-ribonuclease L pathway is a major player in the interferon-induced antiviral defense mechanism of cells. Upon sensing viral dsRNA, 5′-phosphorylated 2′,5′-oligoadenylates are synthesized, and subsequently activate latent RNase L. To determine the influence of 5′-phosphate end on the activation of human RNase L, four sets of 5′-phosphonate modified oligoadenylates were prepared on solid-phase. The ability of these 5′-modified oligoadenylates bearing shortened, isosteric and prolonged phosphonate linkages to activate RNase L was explored. We found that isosteric linkages and linkages prolonged by one atom were in general well tolerated by the enzyme with the EC50 values comparable to that of the natural activator. In contrast, linkages shortened by one atom or prolonged by two atoms exhibited decrease in the activity.

Synthesis and hybridizing property of oligonucleotides including 2′-C,4′-Cethyleneoxy- bridged 2′-deoxyadenosine with an exocyclic methylene unit

2′,4′-Bridged nucleic acids (2′,4′-BNAs) are of interest because oligonucleotides that include them have excellent duplex-forming capability and high nuclease resistance compared to natural oligonucleotides. We have recently developed 2′-C,4′-C-ethyleneoxy-bridged thymidine with an exocyclic methylene unit (methylene-EoDNA-T) as a novel 2′,4′-BNA analog. Oligonucleotides that include methylene-EoDNA-T have marked hybridizing capability, nuclease resistance, and in vitro gene-silencing potency. In the present study, we designed and synthesized a 2′-deoxyadenosine analog of methylene-EoDNA (methylene-EoDNA-A), and incorporated it into oligonucleotides. The results of melting temperature (Tm) analysis of duplexes formed from methylene-EoDNA-A-modified oligonucleotides indicated that the hybridizing capability with regard to complementary DNA was almost the same or slightly higher than that of natural DNA. Moreover, methylene-EoDNA-A:methylene-EoDNA-T base pairs increased the thermal stability of DNA duplexes compared to that of DNA duplexes containing methylene-EoDNA-A- or methylene-EoDNA-T-modification in one strand.

8-substituent-N-methyl-4'-azido-vidarabine analogue and preparation method thereof

The invention discloses a 8-substituent-N-methyl-4'-azido-vidarabine analogue and a preparation method thereof and belongs to the field of pharmaceutical chemistry. The compound has a structural general formula represented by a formula shown in the description, wherein R is Cl, Br or CH3. The 8-substituent-N-methyl-4'-azido-vidarabine analogue is prepared through subjecting adenosine, which serves as a starting raw material, to reactions such as iodination, double-bond forming, azidation, hydroxyl and amino protection, hydroxyl and amino deprotection, Dimorth rearrangement, 8-bit halogenation and methylation sequentially. The 8-substituent-N-methyl-4'-azido-vidarabine analogue is a good potential antitumor drug, the preparation method is simple in operation, the raw materials are cheap, and the cost is low, so that large-scale production is easy to achieve.

Antiviral phosphoramidates

The invention provides novel nucleoside compounds of formula I wherein R1, R2a, R2b, R3, R4, R5, R6, R8a, R9 and R10 are as defined herein which are useful for the treatment of Hepatitis C Virus (HCV) mediated diseases. The invention further provides methods for treatment or prophylaxis of HCV mediated diseases with compounds of formula I and pharmaceutical compositions comprising these compounds,

Antiviral agents

Nucleoside compounds of the formula STR1 wherein: B is a purine or a pyrimidine; X and X' are H, OH or F, provided that at least one is H; Y and Y' are H, OH, OCH3 or F, provided that at least one is H; Y' and Z together form a cyclic phosphate ester, provided that Y is H; or Z is STR2 where n is zero, one, two or three; and Z' is N3 or OCH3 ; provided that when X' and Y' are OH and Z' is N3, B is not cytosine, and when X' and Y' are OH and Z' is OCH3, B is not uracil, adenine or cytosine; and the pharmaceutically acceptable esters, ethers and salts thereof, have been found to have potent antiviral activity with a high therapeutic ratio.

SYNTHESE, STRUCTURE ET REACTIVITE DE SELENOXYDES DERIVES DU RIBOSE ET DE L'ADENOSINE: NOUVELLE VOIE D'ACCES AUX RIBOFURANOSIDES INSATURES EN C(4')-C(5')

A new method for the introduction of an exocyclic double bond at C(4)-C(5) of ribose or adenosine uses the easy conversion of selenoxides to the corresponding alkenes by thermal elimination.Ribose, adenosine and their 2',3'-O-isopropylidene derivatives ha

SIMPLE SYNTHESIS OF 9-(5-DEOXY-β-D-ERYTHRO-PENT-4-ENOFURANOSYL)ADENINE FROM ADENOSINE BY SELENOXIDE FRAGMENTATION

5'-Se-(2-Nitrophenyl)-5'-selenoadenosine (3) was selectively synthesized by the reaction of adenosine with 2-nitrophenylselenocyanate and tri-n-butylphosphine.The selenide 3 was oxidised by treatment with excess hydrogen peroxide to the corresponding sele