14357-08-5

Usage

Uses

Used in Medicinal Chemistry:
N-ethyl-9-pentofuranosyl-9H-purin-6-amine is used as a building block in the synthesis of novel nucleoside analogs for medicinal chemistry. Its unique structure allows for the development of compounds with potential therapeutic properties, contributing to the advancement of pharmaceuticals.
Used in Pharmaceutical Development:
In the pharmaceutical industry, N-ethyl-9-pentofuranosyl-9H-purin-6-amine is utilized as a key component in the creation of new drugs. Its role is to serve as a starting point for the design and synthesis of innovative nucleoside-based therapeutic agents, which may offer improved efficacy and selectivity in treating various diseases.
Further research is essential to fully explore the biological activities and pharmacological applications of N-ethyl-9-pentofuranosyl-9H-purin-6-amine, ensuring its potential is harnessed effectively in the development of new treatments.

Upstream product

• 2004-06-0 6-Chloropurine riboside 
• 75-04-7 ethylamine 
• 75-07-0 acetaldehyde 
• 58-61-7 adenosine 
• 58-63-9 Inosine 
• 5987-73-5 2',3',5'-O-triacetyl-6-chloroinosine 
• 3181-38-2 2',3',5'-tri-O-acetylinosine 
• 74465-47-7 (2R,3R,4R,5R)-2-(acetoxymethyl)-5-(6-bromo-9H-purin-9-yl)tetrahydrofuran-3,4-diyl diacetate 

Downstream Products

• 588698-76-4 5'-O-(4,4'-dimethoxytrityl)-2'-O-(t-butyldimethylsilyl)-N⁶-ethyladenosine 
• 588698-72-0 5'-O-(4,4'-dimethoxytrityl)-N⁶-ethyladenosine 

Relevant academic research and scientific papers

Synthesis of Fluorescent Probes Targeting Tumor-Suppressor Protein FHIT and Identification of Apoptosis-Inducing FHIT Inhibitors

For the early diagnosis of cancer, leading to a better chance of full recovery, marker genes whose expression is already altered in precancerous lesions are desirable, and the tumor-suppressor gene FHIT is one candidate. The gene product, FHIT protein, has a unique dinucleoside triphosphate hydrolase (AP3Aase) activity, and in this study, we designed and synthesized a series of FHIT fluorescent probes utilizing this activity. We optimized the probe structure for high and specific reactivity with FHIT and applied the optimized probe in a screening assay for FHIT inhibitors. Screening of a compound library with this assay identified several hits. Structural development of a hit compound afforded potent FHIT inhibitors. These inhibitors induce apoptosis in FHIT-expressing cancers via caspase activation. Our results support the idea that FHIT binders, no matter whether inhibitors or agonists of AP3Aase activity, might be promising anticancer agents.

Identification of 8-aminoadenosine derivatives as a new class of human concentrative nucleoside transporter 2 inhibitors

Purine-rich foods have long been suspected as a major cause of hyperuricemia. We hypothesized that inhibition of human concentrative nucleoside transporter 2 (hCNT2) would suppress increases in serum urate levels derived from dietary purines. To test this hypothesis, the development of potent hCNT2 inhibitors was required. By modifying adenosine, an hCNT2 substrate, we successfully identified 8-aminoadenosine derivatives as a new class of hCNT2 inhibitors. Compound 12 moderately inhibited hCNT2 (IC50 = 52 ± 3.8 μM), and subsequent structure-activity relationship studies led to the discovery of compound 48 (IC50 = 0.64 ± 0.19 μM). Here we describe significant findings about structural requirements of 8-aminoadenosine derivatives for exhibiting potent hCNT2 inhibitory activity.

α,β-Methylene-ADP (AOPCP) Derivatives and Analogues: Development of Potent and Selective ecto-5′-Nucleotidase (CD73) Inhibitors

ecto-5′-Nucleotidase (eN, CD73) catalyzes the hydrolysis of extracellular AMP to adenosine. eN inhibitors have potential for use as cancer therapeutics. The eN inhibitor α,β-methylene-ADP (AOPCP, adenosine-5′-O-[(phosphonomethyl)phosphonic acid]) was used as a lead structure, and derivatives modified in various positions were prepared. Products were tested at rat recombinant eN. 6-(Ar)alkylamino substitution led to the largest improvement in potency. N6-Monosubstitution was superior to symmetrical N6,N6-disubstitution. The most potent inhibitors were N6-(4-chlorobenzyl)- (10l, PSB-12441, Ki 7.23 nM), N6-phenylethyl- (10h, PSB-12425, Ki 8.04 nM), and N6-benzyl-adenosine-5′-O-[(phosphonomethyl)phosphonic acid] (10g, PSB-12379, Ki 9.03 nM). Replacement of the 6-NH group in 10g by O (10q, PSB-12431) or S (10r, PSB-12553) yielded equally potent inhibitors (10q, 9.20 nM; 10r, 9.50 nM). Selected compounds investigated at the human enzyme did not show species differences; they displayed high selectivity versus other ecto-nucleotidases and ADP-activated P2Y receptors. Moreover, high metabolic stability was observed. These compounds represent the most potent eN inhibitors described to date.

Inhibition of siderophore biosynthesis in Mycobacterium tuberculosis with nucleoside bisubstrate analogues: Structure-activity relationships of the nucleobase domain of 5′-O-[N-(salicyl)sulfamoyl]adenosine

5′-O-[N-(salicyl)sulfamoyl]adenosine (Sal-AMS) is a prototype for a new class of antitubercular agents that inhibit the aryl acid adenylating enzyme (AAAE) known as MbtA involved in biosynthesis of the mycobactins. Herein, we report the structure-based design, synthesis, biochemical, and biological evaluation of a comprehensive and systematic series of analogues, exploring the structure-activity relationship of the purine nucleobase domain of Sal-AMS. Significantly, 2-phenyl-Sal-AMS derivative 26 exhibited exceptionally potent antitubercular activity with an MIC99 under iron-deficient conditions of 0.049 μM while the N-6-cyclopropyl-Sal-AMS 16 led to improved potency and to a 64-enhancement in activity under iron-deficient conditions relative to iron-replete conditions, a phenotype concordant with the designed mechanism of action. The most potent MbtA inhibitors disclosed here display in vitro antitubercular activity superior to most current first line TB drugs, and these compounds are also expected to be useful against a wide range of pathogens that require aryl-capped siderphores for virulence.

Substrate analogues for an RNA-editing adenosine deaminase: Mechanistic investigation and inhibitor design

ADARs are adenosine deaminases that act on RNA and are responsible for RNA-editing reactions that occur in eukaryotic mRNAs, including the mRNAs of glutamate and serotonin receptors. ADARs capable of editing biologically relevant RNA substrates have been

Anti-HCV nucleoside derivatives

The present invention comprises novel and known purine and pyrimidine nucleoside derivatives which have been discovered to be active against hepatitis C virus (HCV). The use of these derivatives for the treatment of HCV infection is claimed as are the novel nucleoside derivatives disclosed herein.

Reductive monoalkylation of aromatic amines via amidine intermediates

The convenience and efficiency of using amidines as intermediates in the reductive monoalkylation of aromatic amines has been demonstrated. This monoalkylation can be performed as either a two-step synthesis or a one-pot procedure. Several examples are presented which clearly demonstrate the utility of this new method for the methylation or ethylation of aromatic amines, including unprotected nucleosides.

Adenosine analogues as inhibitors of Trypanosoma brucei phosphoglycerate kinase: Elucidation of a novel binding mode for a 2-Amino-N6-substituted adenosine

As part of a project aimed at structure-based design of adenosine analogues as drugs against African trypanosomiasis, N6-, 2-amino-N6-, and N2-substituted adenosine analogues were synthesized and tested to establish structure - activity relationships for inhibiting Trypanosoma brucei glycosomal phosphoglycerate kinase (PGK), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), and glycerol-3-phosphate dehydrogenase (GPDH). Evaluation of X-ray structures of parasite PGK, GAPDH, and GPDH complexed with their adenosyl-bearing substrates led us to generate a series of adenosine analogues which would target all three enzymes simultaneously. There was a modest preference by PGK for N6-substituted analogues bearing the 2-amino group. The best compound in this series, 2-amino-N6-[2-(p-hydroxyphenyl)ethyl]adenosine (46b), displayed a 23-fold improvement over adenosine with an IC50 of 130 μM. 2-[[2-(p-Hydroxyphenyl)ethyl]amino]adenosine (46c) was a weak inhibitor of T. brucei PGK with an IC50 of 500 μM. To explore the potential of an additive effect that having the N6 and N2 substitutions in one molecule might provide, the best ligands from the two series were incorporated into N6,N2-disubstituted adenosine analogues to yield N6-(2-phenylethyl)-2-[(2-phenylethyl)amino]adenosine (69) as a 30 μM inhibitor of T. brucei PGK which is 100-fold more potent than the adenosine template. In contrast, these series gave no compounds that inhibited parasitic GAPDH or GPDH more than 10-20% when tested at 1.0 mM. A 3.0 A? X-ray structure of a T. brucei PGK/46b complex revealed a binding mode in which the nucleoside analogue was flipped and the ribosyl moiety adopted a syn conformation as compared with the previously determined binding mode of ADP. Molecular docking experiments using QXP and SAS program suites reproduced this 'flipped and rotated' binding mode.

Anti-dementia agents

An anti-dementia agent comprising as an active ingredient an adenosine derivative is disclosed. The anti-dementia agent is useful in the therapy of various types of dementia, especially senile dementia. Examples of the adenosine derivative include L-N6 -phenylisopropyl-adenosine, 2-chloroadenosine, N6 -cyclohexyladenosine, adenosine-5'-(N-cyclopropyl)carboxamide.

1,N6-Etheno-Bridged Adenines and Adenosines. Alkyl Substitution, Fluorescence Properties, and Synthetic Applications

It has been shown that the reaction of chloroacetaldehyde with adenosine at pH 4.5 and 37 deg C that produces the fluorescent ε-adenosine species will not develop interfering fluorescence with N6-alkyladenosines.The preferred site of methylation and benzylation of ε-adenosine and ε-adenine was established as N(9) (a) by acidic ring opening of the products to substituted aminobiimidazoles in which the two etheno protons were nonequivalent; (b) by reaction of N6-substituted adenines with chloroacetaldehyde followed by polyphosphoric acid to dehydrate the intermediate to an N(9)-substituted ε-adenine for an unequivocal synthesis.The fluorescence of the ε-adenosine and ε-adenine species at pH 7.0 has again been confirmed, and the fluorescence properties of their N(9)-alkylated derivatives under neutral and acidic conditions have been determined.It has been shown possible, earlier reports to the contrary, to prepare N6-substituted adenosines through Schiff-base formation on the 6-NH2.The general method involves the use of sodium cyanohydridoborate to bring about reductive amination of aldehydes and ketones at acidic pH and is exemplified by the synthesis of N6-ethyladenosine, N6-benzyladenosine, and N6-furfuryladenosine (kinetin riboside), using large excesses of aldehyde and reducing agent.