20125-39-7

Usage

Uses

Used in Pharmaceutical Industry:
N6-(2-PHENYLETHYL)ADENOSINE is used as an anti-proliferative agent for bladder cancer treatment due to its ability to inhibit the growth and proliferation of cancer cells. Its interaction with the human A3 adenosine receptor makes it a potential therapeutic option for targeting bladder cancer specifically.
Additionally, as a potent ligand at the human A3 adenosine receptor, N6-(2-PHENYLETHYL)ADENOSINE may have potential applications in other areas of pharmaceutical research, such as the development of new drugs targeting adenosine receptors for various therapeutic purposes.

InChI:InChI=1/C18H21N5O4/c24-8-12-14(25)15(26)18(27-12)23-10-22-13-16(20-9-21-17(13)23)19-7-6-11-4-2-1-3-5-11/h1-5,9-10,12,14-15,18,24-26H,6-8H2,(H,19,20,21)

Upstream product

• 7440-44-0 pyrographite 
• 64-04-0 phenethylamine 
• 58-63-9 inosine 
• 7387-58-8 6-N-2',3',5'-tri-O-tetraacetyladenosine 
• 60-12-8 2-phenylethanol 
• 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 
• 2004-06-0 6-Chloropurine riboside 

Downstream Products

• 901776-23-6 ((3aR,4R,6R,6aR)-2,2-dimethyl-6-(6-(phenethylamino)-9H-purin-9-yl)-tetrahydrofuro[3,4-d][1,3]dioxol-4-yl)methanol 

Relevant academic research and scientific papers

A molecular target for suppression of the evolution of antibiotic resistance: Inhibition of the Escherichia coli RecA protein by N 6-(1-naphthyl)-ADP

We report that N6-(1-naphthyl)-ADP (1) inhibits the Escherichia coli RecA protein in vitro. A novel rapid screen identified 1 as a potent inhibitor of RecA nucleoprotein filament formation, and further characterization established 1 as an ATP-competitive inhibitor of RecA-catalyzed ATP hydrolysis. 1 and other inhibitors of RecA activities represent a new approach for understanding the molecular targets and pathways involved in the evolution of antibiotic resistance in bacteria.

Rational Design of Selective Adenine-Based Scaffolds for Inactivation of Bacterial Histidine Kinases

Bacterial histidine kinases (HKs) are quintessential regulatory enzymes found ubiquitously in bacteria. Apart from their regulatory roles, they are also involved in the production of virulence factors and conferring resistance to various antibiotics in pathogenic microbes. We have previously reported compounds that inhibit multiple HKs by targeting the conserved catalytic and ATP-binding (CA) domain. Herein, we conduct a detailed structure-activity relationship assessment of adenine-based inhibitors using biochemical and docking methods. These studies have resulted in several observations. First, interaction of an inhibitor's amine group with the conserved active-site Asp is essential for activity and likely dictates its orientation in the binding pocket. Second, a N-NH-N triad in the inhibitor scaffold is highly preferred for binding to conserved Gly:Asp:Asn residues. Lastly, hydrophobic electron-withdrawing groups at several positions in the adenine core enhance potency. The selectivity of these inhibitors was tested against heat shock protein 90 (HSP90), which possesses a similar ATP-binding fold. We found that groups that target the ATP-lid portion of the catalytic domain, such as a six-membered ring, confer selectivity for HKs.

Modification of the length and structure of the linker of N6-benzyladenosine modulates its selective antiviral activity against enterovirus 71

Very recently, we demonstrated that N6-isopentenyladenosine, a cytokinin nucleoside, exerts a potent and selective antiviral effect on the replication of human enterovirus 71. The present study is devoted to the structure optimization of another natural compound: N6-benzyladenosine. We mainly focused on the exploration of the size and nature of the linker between the adenine and the phenyl ring, as well as on the necessity of the D-ribose residue. More than 30 analogues of N6-benzyladenosine were prepared and their antiviral properties were evaluated. Two main methodologies were used for preparation: N6-acetyl-2′,3′,5′-tri-O-acetyladenosine can be regioselectively alkylated either by alkyl halides under base promoted conditions or by alcohols in Mitsunobu reactions. After deacylation with 4 M PrNH2 in MeOH at room temperature for one day, the desired products were obtained in overall high yields. Analysis of the structure-activity relationship clearly shows that the optimal size of the linker is limited to 2 or 3 atoms (compounds 4-7). 2′-Deoxyadenosine derivatives did not elicit any inhibitory or cytotoxic effect, while 5′-deoxynucleosides still induced some cell protective antiviral activity. Based on these observations, it can be hypothesized that there may be another mechanism that is at the base of the antiviral activity of these compounds against enterovirus 71 besides a possible 5′-triphosphorylation followed by a putative inhibitory effect on RNA synthesis.

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.

N6-Alkyladenosines: Synthesis and evaluation of in vitro anticancer activity

A series of adenosine analogues differently substituted in N 6-position were synthesized to continue our studies on the relationships between structure and biological activity of iPA. The structures of the compounds were confirmed by standard studies of 1H NMR, MS and elemental analysis. These molecules were then evaluated for their anti-proliferative activity on bladder cancer cells. We found that some of these compounds possess anti-proliferative activity but have no effect on cell invasion and metalloprotease activity.

Inhibitors of DNA Methyltransferase

The invention relates to the inhibition of DNA methyltransferase isoforms DNMT1 and DNMT3b2. The invention provides compounds and methods for inhibiting DNMT1 and DNMT3b2.

Inhibitors of RecA activities for control of antibiotic-resistant bacterial pathogens

Compounds for modulating RecA protein activity are provided. In some embodiments, the compounds modulate RecA activity by interfering with assembly of monomeric RecA protein subunits into a nucleoprotein filament. In some embodiments, the compounds modulate RecA activity by interfering with adenosine triphosphate hydrolysis by the RecA protein. Methods of screening for and methods of using the compounds are also provided.

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.