2620-62-4

Usage

Uses

1. Used in Organic Synthesis:
N6,N6-DIMETHYLADENOSINE is used as a key compound in organic synthesis for the development of various chemical products and materials. Its unique structure and properties make it a valuable building block in the synthesis of complex organic molecules.
2. Used in Pharmaceutical Industry:
N6,N6-DIMETHYLADENOSINE is used as an intermediate in the synthesis of various pharmaceutical compounds. Its unique chemical properties allow it to be a versatile component in the development of new drugs and therapeutic agents.
3. Used in Research and Development:
N6,N6-DIMETHYLADENOSINE is used as a research tool in the study of adenosine-related biological processes and pathways. Its unique structure provides insights into the role of methylation in the regulation of gene expression and cellular function.
4. Used in Chemical Analysis:
N6,N6-DIMETHYLADENOSINE is used as a reference compound in various analytical techniques, such as chromatography and mass spectrometry, to help identify and quantify similar compounds in complex mixtures.

InChI:InChI=1/C12H17N5O4/c1-16(2)10-7-11(14-4-13-10)17(5-15-7)12-9(20)8(19)6(3-18)21-12/h4-6,8-9,12,18-20H,3H2,1-2H3/t6-,8-,9-,12-/m1/s1

Upstream product

• 17287-03-5 trimethylsulphonium hydroxide 
• 58-61-7 adenosine 
• 14426-53-0 6-Iodo-purine riboside 
• 124-40-3 dimethyl amine 
• 2004-06-0 6-Chloropurine riboside 
• 68-12-2 N,N-dimethyl-formamide 
• 5991-01-5 2,3,5-(tri-O-benzoyl)-D-ribofuranosyl chloride 
• 105499-44-3 2,3,5-tri-O-acetyl-α-D-ribofuranosyl chloride 
• 6974-32-9 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose 
• 163632-54-0 9-(β-D-ribofuranosyl)-6-(1,2,4-triazol-4-yl)purine 
• 7387-57-7 triacetyladenosine 
• 3181-38-2 2',3',5'-tri-O-acetylinosine 
• 58-63-9 Inosine 
• 5987-73-5 2',3',5'-O-triacetyl-6-chloroinosine 

Downstream Products

• 128612-09-9 2'-O-Trityl-N⁶,N⁶-dimethyladenosine 
• 19083-21-7 2',3'-O-Isopropylidene-N⁶,N⁶-dimethyladenosine 
• 128636-80-6 3',5'-Di-O-trityl-N⁶,N⁶-dimethyladenosine 
• 128612-08-8 2',5'-Di-O-trityl-N⁶,N⁶-dimethyladenosine 
• 1867-73-8 N⁶-methyladenosine 
• 58-61-7 adenosine 
• 19083-21-7 2',3'-O-isopropylidene-N₆,N₆'-dimethyladenosine 
• 15502-55-3 5'-O-Benzoyl-N⁶,N⁶-dimethyl-2'3'-O-isopropylideneadenosine 
• 15087-42-0 5'-O-Benzoyl-N⁶,N⁶-dimethyladenosine 
• 74397-42-5 2-{1-Benzyl-2-[(2R,3R,4R,5R)-2-(6-dimethylamino-purin-9-yl)-4-hydroxy-5-trityloxymethyl-tetrahydro-furan-3-yloxy]-ethyl}-isoindole-1,3-dione 
• 74397-39-0 2-{1-Benzyl-2-[(2R,3S,4R,5R)-5-(6-dimethylamino-purin-9-yl)-4-hydroxy-2-trityloxymethyl-tetrahydro-furan-3-yloxy]-ethyl}-isoindole-1,3-dione 
• 74397-45-8 2-{1-[(2R,3S,4R,5R)-5-(6-Dimethylamino-purin-9-yl)-4-hydroxy-2-hydroxymethyl-tetrahydro-furan-3-yloxymethyl]-2-phenyl-ethyl}-isoindole-1,3-dione 
• 74635-46-4 S-(N⁶,N⁶-dimethyladenosyl)-L-methionine 
• 70230-68-1 5-(Methylamino)-1-(2,3,5-tri-O-benzyl-β-D-ribofuranosyl)imidazole-4-carboxamide 

Relevant academic research and scientific papers

Adenosine N1-oxide analogues as inhibitors of orthopox virus replication

Several new types of adenosine N1-oxide (ANO) derivatives including N1-alkoxy and N6-alkyl as well as the analogues with a trihydroxycyclopentane ring in place of the ribose residue were synthesized and their antiviral properties were evaluated in Vero and LLC-MK2 cell cultures infected with vaccinia, mousepox, monkeypox, cowpox, and different isolates of smallpox viruses. The antiviral activity of ANO and its derivatives significantly depended on the virus type and cell cultures. Mousepox and monkeypox viruses were the most sensitive to these compounds, while vaccinia and cowpox viruses were inhibited at the concentrations 1-1.5 orders of magnitude higher. The toxicity of the synthesized compounds was much lower than that of ANO. Modifications of the ANO N6-position did not offer any advantages over the parent compound. The synthesized N1-oxide derivatives of noraristeromycin retained the activity comparable with noraristeromycin and displayed a decreased toxicity. No direct correlation between antiviral activity and stability of the compounds was found.

6-Iodopurine as a Versatile Building Block for RNA Purine Architecture Modifications

Natural modified bases in RNA were found to be indispensable for basic biological processes. In addition, artificial RNA modifications have been a versatile toolbox for the study of RNA interference, structure, and dynamics. Here, we present a chemical method for the facile synthesis of RNA containing C6-modified purine. 6-Iodopurine, as a postsynthetic building block with high reactivity, was used for metal-free construction of C-N, C-O, and C-S bonds under mild conditions and C-C bond formation by Suzuki-Miyaura cross-coupling. Our strategy provides a convenient approach for the synthesis of various RNA modifications, especially for oligonucleotides containing specific structures.

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.

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.

OLIGONUCLEOTIDE HAVING NON-NATURAL NUCLEOTIDE AT 5'-TERMINAL THEREOF

An oligonucleotide having a nucleotide residue or a nucleoside residue represented by formula (I) {wherein X1 is an oxygen atom or the like, R1 is formula (IIA) (wherein R5A is halogen or the like, and R6A is a hydrogen atom or the like), formula (IVA) (wherein Y3A is a nitrogen atom or the like, and Y4A is CH or the like), or the like, R2 is a hydrogen atom, hydroxy, halogen, or optionally substituted lower alkoxy, and R3 is a hydrogen atom or the like, or formula (VI) (wherein n2 is 1, 2 or 3)} at the 5′ end thereof, wherein the nucleotide residue or the nucleoside residue binds to an adjacent nucleotide residue through the oxygen atom at position 3, is provided.

OLIGONUCLEOTIDE

The present invention provides an oligonucleotide having improved affinity for AGO2, and the like. The oligonucleotide has a nucleotide residue or a nucleoside residue represented by formula (I) {wherein X1 is an oxygen atom or the like, R1 is formula (IIA) (wherein R5A is halogen or the like, and R6A is a hydrogen atom or the like) or formula (IVA) (wherein Y3A is a nitrogen atom or the like, and Y4A is CH or the like), or the like, R2 is a hydrogen atom, hydroxy, halogen, or optionally substituted lower alkoxy, and R3 is a hydrogen atom or the like} at the 5′ end thereof, and the nucleotide residue or the nucleoside residue binds to an adjacent nucleotide residue through the oxygen atom at position 3.

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.

2-Hexylthio-β,γ-CH2-ATP is an effective and selective NTPDase2 inhibitor

NTPDase2 catabolizes nucleoside triphosphates and consequently, through the interaction of nucleotides with P2 receptors, controls multiple biological responses. NTPDase2 inhibitors could modulate responses induced by nucleotides in thrombosis, inflammation, cancer, etc. Here we developed a set of ATP analogues as potential NTPDase inhibitors and identified a subtype-selective and potent NTPDase2 inhibitor, 2-hexylthio-β,γ-methylene-ATP, 2. Analogue 2 was stable to hydrolysis by NTPDase1, -2, -3, and -8. It inhibited hNTPDase2 with Ki 20 μM, while only marginally (5-15%) inhibiting NTPDase1, -3, and -8. Homology models of hNTPDase1 and -2 were constructed. Docking and subsequent linear interaction energy (LIE) simulations provided a correlation with r2 = 0.94 between calculated and experimental inhibition data for the triphosphate analogues considered in this work. The origin of selectivity of 2 for NTPDase2 over NTPDase1 is the thiohexyl moiety of 2 which is favorably located within a hydrophobic pocket, whereas in NTPDase1 it is exposed to the solvent.

The optimized microwave-assisted decomposition of formamides and its synthetic utility in the amination reactions of purines

The microwave-assisted decomposition of DMF was thoroughly studied and the reaction conditions (temperature, solvent effect, and effect of additives, such as acids, bases, and salts) were optimized for its use in amination reactions. The applicability of this expedient methodology in purine chemistry and with various formamides is demonstrated.

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.