3001-45-4

Usage

Uses

Used in Pharmaceutical Industry:
8-Mercaptoadenosine is used as a therapeutic agent for its anti-inflammatory and immunomodulatory properties, targeting various conditions such as cancer, autoimmune diseases, and inflammatory disorders. It is valued for its ability to modulate the activity of enzymes in the inflammatory response and to affect the production of signaling molecules in the immune system, offering a potential treatment for a wide array of health issues.
Used in Cancer Treatment:
8-Mercaptoadenosine is used as a potential anti-cancer agent, where its effects on inflammatory and immune responses may contribute to the management or treatment of cancerous conditions. Its interaction with molecular targets could provide a novel approach to cancer therapy.
Used in Autoimmune Disease Management:
In the context of autoimmune diseases, 8-Mercaptoadenosine is used as an immunomodulatory agent to help regulate the immune system's response, potentially leading to the mitigation of symptoms and disease progression.
Used in Inflammatory Disorder Treatment:
8-Mercaptoadenosine is utilized as an anti-inflammatory agent for the treatment of various inflammatory disorders, leveraging its capacity to modulate inflammatory responses and alleviate associated symptoms.

InChI:InChI=1/C10H13N5O4S/c11-7-4-8(13-2-12-7)15(10(20)14-4)9-6(18)5(17)3(1-16)19-9/h2-3,5-6,9,16-18H,1H2,(H,14,20)(H2,11,12,13)

Upstream product

• 2946-39-6 8-bromoadenosine 
• 17356-08-0 thiourea 
• 6974-32-9 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose 
• 7390-62-7 6-amino-7,9-dihydro-8H-purine-8-thione 

Downstream Products

• 104343-41-1 8-<<2-hydroxy-3-(p-ethoxycarbonyl)phenoxypropyl>thio> adenosine 
• 62475-47-2 (5'R)-5',8-cycloadenosine 
• 58-63-9 inosine 
• 58-61-7 adenosine 
• 2946-39-6 8-bromoadenosine 
• 16667-76-8 8,2'-S-cyclo-adenosine 
• 13389-13-4 8-Methylaminoadenosine 
• 34408-14-5 8-chloroadenosine 
• 147538-91-8 8-<<3-(p-isobutoxycarbonyl)phenoxy-2-oxo-propyl>thio> adenosine 

Relevant academic research and scientific papers

Novel inhibitors of nucleoside triphosphate diphosphohydrolases: Chemical synthesis and biochemical and pharmacological characterizations

To elucidate the physiological role played by nucleoside triphosphate diphosphohydrolase (NTPDase; EC 3.6.1.5), adenine nucleotide analogues, modified on the purine ring, hay e been synthesized and tested as potential inhibitors. Resistance of ATp analogues to hydrolysis and their potency as NTPDase inhibitors were evaluated. For this purpose, a particulate fraction isolated from bovine spleen was used as the enzyme source. Among the synthesized analogues; 8-thiobutyladenosine 5'-triphosphate (8-BuS-ATP) was found to be the most effective nonhydrolyzable competitive inhibitor, with an estimated K(i) of 10 μM. This nonhydrolyzable analogue did not exert any P2X-receptor-mediated effect on endothelium-denuded blood vessels, from the guinea pig mesenteric bed. In agreement with this observation, infusion of the analogue did not cause any significant blood pressure variations of the precontracted vessel. Because in previous studies on isolated turkey erythrocytes and rat astrocytes 8-BuS-ATP was not able to trigger any P2Y1- receptor-mediated effect, it therefore appears that this NTPDase inhibitor does not interfere with purinergic receptors.

Highly potent and selective ectonucleotide pyrophosphatase/ phosphodiesterase i inhibitors based on an adenosine 5′-(α or γ)-Thio-(α,β- or β,γ)-methylenetriphosphate scaffold

Aberrant nucleotide pyrophosphatase/phosphodiesterase-1 (NPP1) activity is associated with chondrocalcinosis, osteoarthritis, and type 2 diabetes. The potential of NPP1 inhibitors as therapeutic agents, and the scarceness of their structure-activity relat

Prebiotic Photochemical Coproduction of Purine Ribo- And Deoxyribonucleosides

The hypothesis that life on Earth may have started with a heterogeneous nucleic acid genetic system including both RNA and DNA has attracted broad interest. The recent finding that two RNA subunits (cytidine, C, and uridine, U) and two DNA subunits (deoxyadenosine, dA, and deoxyinosine, dI) can be coproduced in the same reaction network, compatible with a consistent geological scenario, supports this theory. However, a prebiotically plausible synthesis of the missing units (purine ribonucleosides and pyrimidine deoxyribonucleosides) in a unified reaction network remains elusive. Herein, we disclose a strictly stereoselective and furanosyl-selective synthesis of purine ribonucleosides (adenosine, A, and inosine, I) and purine deoxynucleosides (dA and dI), alongside one another, via a key photochemical reaction of thioanhydroadenosine with sulfite in alkaline solution (pH 8-10). Mechanistic studies suggest an unexpected recombination of sulfite and nucleoside alkyl radicals underpins the formation of the ribo C2′-O bond. The coproduction of A, I, dA, and dI from a common intermediate, and under conditions likely to have prevailed in at least some primordial locales, is suggestive of the potential coexistence of RNA and DNA building blocks at the dawn of life.

Nucleotide Analog ARL67156 as a Lead Structure for the Development of CD39 and Dual CD39/CD73 Ectonucleotidase Inhibitors

Nucleoside triphosphate diphosphohydrolase1 (NTPDase1, CD39) inhibitors have potential as novel drugs for the (immuno)therapy of cancer. They increase the extracellular concentration of immunostimulatory ATP and reduce the formation of AMP, which can be further hydrolyzed by ecto-5’-nucleotidase (CD73) to immunosuppressive, cancer-promoting adenosine. In the present study, we synthesized analogs and derivatives of the standard CD39 inhibitor ARL67156, a nucleotide analog which displays a competitive mechanism of inhibition. Structure-activity relationships were analyzed at the human enzyme with respect to substituents in the N6- and C8-position of the adenine core, and modifications of the triphosph(on)ate chain. Capillary electrophoresis coupled to laser-induced fluorescence detection employing a fluorescent-labeled ATP derivative was employed to determine the compounds’ potency. Selected inhibitors were additionally evaluated in an orthogonal, malachite green assay versus the natural substrate ATP. The most potent CD39 inhibitors of the present series were ARL67156 and its derivatives 31 and 33 with Ki values of around 1 μM. Selectivity studies showed that all three nucleotide analogs additionally blocked CD73 acting as dual-target inhibitors. Docking studies provided plausible binding modes to both targets. The present study provides a full characterization of the frequently applied CD39 inhibitor ARL67156, presents structure-activity relationships, and provides a basis for future optimization towards selective CD39 and dual CD39/CD73 inhibitors.

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.

Coumarin-purine ribofuranoside conjugates as new agents against hepatitis c virus

About 3% of world's population is infected by the hepatitis C virus (HCV), for which prophylactic vaccine is not available yet. Nowadays, pegylated interferon-α and ribavirin are commonly used to treat HCV; unfortunately these drugs often produce significant side effects. Upon the desperate need of anti-HCV drugs, a plan to establish a new compound library was set that included leads with high antiviral activity, good hydrophilicity, yet low toxicity. Accordingly, 26 new conjugated compounds were synthesized through the chemical coupling of various 9-(β-d-ribofuranosyl)purine-8-thiones with 3-(chloromethyl)coumarins bearing various substituents. A SCH2 unit was used to link the coumarin and the purine moieties. The three hydroxyl groups at the 2′-, 3′-, and 5′-positions were selectively protected with an acyl or acetal group in these coumarin-purine ribofuranosides. Their anti-HCV and cytostatic determination assays were performed, and the structure-activity relationship was established. Three conjugates in the family of 8-(coumarin-3′-yl)methylthio-9-(β-d-ribofuranos-1′-yl)purine possessed an appealing ability to inhibit HCV replication with EC50 between 5.5 and 6.6 μM and EC90 of 20 μM. These data in the new compound library provide clues for the future in the development of anti-HCV leads for viral eradication.

High-throughput five minute microwave accelerated glycosylation approach to the synthesis of nucleoside libraries

The Vorbrueggen glycosylation reaction was adapted into a one-step 5 min/130 °C microwave assisted reaction. Triethanolamine in acetontrile containing 2% water was determined to be optimal for the neutralization of trimethylsilyl inflate allowing for direct MPLC purification of the reaction mixture. When coupled with a NH3/methanol deprotection reaction, a high-throughput method of nucleoside library synthesis was enabled. The method was demonstrated by examining the ribosylation of 48 nitrogen containing heteroaromatic bases that included 25 purines, four pyrazolopyrimidines, two 8-azapurines, one 2-azapurine, two imidazopyridines, two benzimidazoles, three imidazoles, three 1,2,4-triazoles, two pyrimidines, two 3-deazapyrimidines, one quinazolinedione, and one alloxazine. Of these, 32 yielded single regioisomer products, and six resulted in separable mixtures. Seven examples provided inseparable regioisomer mixtures of -two to three compounds (16 nucleosides), and three examples failed to yield isolable products. For the 45 single isomers isolated, the average two-step overall yield ± SD was 26 ± 16%, and the average purity ± SD was 95 ± 6%. A total of 58 different nucleosides were prepared of which 15 had not previously been accessed directly from glycosylation/deprotection of a readily available base.

C8-substituted purine nucleotide analogs

C8-substituted purine nucleotide analogs, such as ATP analogs, and their use is described, including their use as inhibitors of NTPDases and thereby as tools to modulate the conversion of nucleotides into nucleoside derivatives, and thus modulate the levels of these compounds. Such modulation further provides for the modulation of the activity and function of many processes which are affected by these compounds.

Molecular recognition of modified adenine nucleotides by the P2Y1-receptor. 1. A synthetic, biochemical, and NMR approach

The remarkably high potencies of 2-thioether-adenine nucleotides regarding the activation of the P2Y1-receptor (P2Y1-R) in turkey erythrocyte membranes represent some of the largest substitution-promoted increases in potencies over that of a natural receptor ligand. This paper describes the investigation regarding the origin of the high potency of these P2Y1-R ligands over that of ATP. For this study, an integrated approach was employed combining the synthesis of new ATP analogues, their biochemical evaluation, and their SAR analysis involving NMR experiments and theoretical calculations. These experiments and calculations were performed to elucidate the conformation and to evaluate the electronic nature of the investigated P2Y1-R ligands. ATP analogues synthesized included derivatives where C2 or C8 positions were substituted with electron-donating groups such as ethers, thioethers, or amines. The compounds were tested for their potency to induce P2Y1-R-mediated activation of phospholipase C in turkey erythrocytes and Ca2+ response in rat astrocytes. 8-Substituted ATP and AMP derivatives had little or no effect on phospholipase C or on calcium levels, whereas the corresponding 2-substituted ATP analogues potently increased the levels of inositol phosphates and [Ca2+](i). AMP analogues were ineffective except for 2-butylthio-AMP which induced a small Ca2+ response. P2Y1-R activity of these compounds was demonstrated by testing these ligands also on NG108-15 neuroblastoma x glioma hybrid cells. NMR data together with theoretical calculations imply that steric, rather than electronic, effects play a major role in ligand binding to the P2Y1-R. Hydrophobic interactions and H-bonds of the C2 substituent appear to be important determinants of a P2Y1-R ligand affinity.