19234-66-3

Usage

Uses

Used in Pharmaceutical Industry:
2',3'-O-Isopropylidene-Adenosine-5'-carboxylic Acid is used as a key intermediate in the synthesis of nucleosides, specifically adenosine A3 receptor agonists. These agonists play a crucial role in the development of drugs targeting various diseases, including inflammation, asthma, and neurodegenerative disorders.
Used in Research and Development:
In the field of research and development, 2',3'-O-Isopropylidene-Adenosine-5'-carboxylic Acid serves as an essential compound for studying the structure and function of adenosine receptors. This knowledge contributes to the advancement of drug discovery and the development of novel therapeutic strategies.
Used in Chemical Synthesis:
2',3'-O-Isopropylidene-Adenosine-5'-carboxylic Acid is also utilized in chemical synthesis processes, where it can be further modified or used as a building block to create more complex molecules with specific biological activities. This makes it a valuable asset in the synthesis of various pharmaceutical compounds and other specialty chemicals.

Upstream product

• 159647-45-7 (3aS,4S,6R,6aR)-6-(6-Amino-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxole-4-carboxylic acid 4-nitro-phenyl ester 
• 69530-93-4 5'-(O-tert-butyldimethylsilyl)adenosine 
• 362-75-4 2',3'-isopropylidene adenosine 
• 58-61-7 adenosine 

Downstream Products

• 23754-29-2 2',3'-O-isopropylideneadenosine-5'-carboxylic acid methyl ester 
• 3415-09-6 adenosine 5'-carboxylic acid 
• 72758-39-5 (3aS,4S,6R,6aR)-6-(6-Amino-purin-9-yl)-2,2-dimethyl-tetrahydro-furo[3,4-d][1,3]dioxole-4-carboxylic acid phenylamide 
• 39491-51-5 5'-N-methyl-2',3'-O-isopropylidenecarboxamidoadenosine 
• 58048-28-5 5'-N-cyclopropyl-2',3'-O-isopropylidenecarboxamidoadenosine 
• 28440-13-3 (3aS,4S,6R,6aR)-2,2-dimethyl-6-(6-oxo-1,6-dihydro-9H-purin-9-yl)tetrahydrofuro[3,4-d][1,3]dioxole-4-carboxylic acid 
• 937018-48-9 N-[2-[[4-[4-(4-aminophenyl)buta-1,3-dienyl]phenyl]ethylamino]ethyl]-1-(6-amino-9H-purin-9-yl)-1-deoxy-2,3-O-(1-methylethylidene)-β-D-ribofuranuronamide 
• 72758-43-1 adenosine-5'-(N-phenylcarboxamide) 
• 851046-50-9 C₂₃H₂₄N₆O₆ 
• 851046-48-5 C₂₁H₂₂N₆O₆ 
• 1106998-86-0 2',3'-O-isopropylideneadenosine-4'-dehydroxymethyl-4'-carboxylic acid 6-aminohexanoic acid benzyl ester conjugate 
• 1174010-25-3 C₄₈H₅₉N₂₁O₁₂ 
• 1174010-31-1 C₃₈H₅₇N₂₁O₁₂ 
• 1174010-37-7 C₄₆H₆₅N₂₃O₁₃S 

Relevant academic research and scientific papers

Potent SARS-CoV-2 mRNA Cap Methyltransferase Inhibitors by Bioisosteric Replacement of Methionine in SAM Cosubstrate

Viral mRNA cap methyltransferases (MTases) are emerging targets for the development of broad-spectrum antiviral agents. In this work, we designed potential SARS-CoV-2 MTase Nsp14 and Nsp16 inhibitors by using bioisosteric substitution of the sulfonium and amino acid substructures of the cosubstrate S-adenosylmethionine (SAM), which serves as the methyl donor in the enzymatic reaction. The synthetically accessible target structures were prioritized using molecular docking. Testing of the inhibitory activity of the synthesized compounds showed nanomolar to submicromolar IC50 values for five compounds. To evaluate selectivity, enzymatic inhibition of the human glycine N-methyltransferase involved in cellular SAM/SAH ratio regulation was also determined, which indicated that the discovered compounds are nonselective inhibitors of the studied MTases with slight selectivity for Nsp16. No cytotoxic effects were observed; however, this is most likely a result of the poor cell permeability of all evaluated compounds.

Synthesis of 5'-N-(2-[18F]Fluoroethyl)-carboxamidoadenosine: A promising tracer for investigation of adenosine receptor system by PET technique

5'-N-(2-[18F]Fluoroethyl)-carboxainidoadenosine ([18F]FNECA), a promising 18F-labelled adenosine agonist has been prepared by two different synthetic routes. In the first, [18F]fluoride was reacted with 5'-N,N-ethylene-2',3'-O-isopropylidenecarboxamido-adenosine and after removing the protective group [18F]FNECA was obtained in a low radiochemical yield (1 ± 1%, mean ± sd, n = 7, decay corrected). In the second, 2-[18F]fluoroethylamine was synthesised according to the literature and reacted with 2',3'-O-isopropylideneadenosine-5'-uronic acid in the presence of a coupling agent. The following hydrolysis step provided the [18F]FNECA with a modest radiochemical yield (24 ± 9%, n = 17, based on [18F]fluoride-activity). After purification by preparative reverse phase HPLC 18.9-166.5 MBq (0.51-4.5 mCi) [18F]FNECA was obtained with a specific activity of 2.35 ± 1.14 TBq/mmol (63.5 ± 30.9 Ci/mmol, n = 3). The total synthesis took 200 min and the decay corrected radiochemical yield based on [18F]F- activity was 17 ± 9% (n = 5) with more than 99.9% radiochemical purity. This second route provides sufficient [18F]FNECA for the subsequent biological evaluation using PET-technique.

Avoiding Antibiotic Inactivation in Mycobacterium tuberculosis by Rv3406 through Strategic Nucleoside Modification

5′-[N-(d-biotinoyl)sulfamoyl]amino-5′-deoxyadenosine (Bio-AMS, 1) possesses selective activity against Mycobacterium tuberculosis (Mtb) and arrests fatty acid and lipid biosynthesis through inhibition of the Mycobacterium tuberculosis biotin protein ligase (MtBPL). Mtb develops spontaneous resistance to 1 with a frequency of at least 1 × 10-7 by overexpression of Rv3406, a type II sulfatase that enzymatically inactivates 1. In an effort to circumvent this resistance mechanism, we describe herein strategic modification of the nucleoside at the 5′-position to prevent enzymatic inactivation. The new analogues retained subnanomolar potency to MtBPL (KD = 0.66-0.97 nM), and 5′R-C-methyl derivative 6 exhibited identical antimycobacterial activity toward: Mtb H37Rv, MtBPL overexpression, and an isogenic Rv3406 overexpression strain (minimum inhibitory concentration, MIC = 1.56 μM). Moreover, 6 was not metabolized by recombinant Rv3406 and resistant mutants to 6 could not be isolated (frequency of resistance -10) demonstrating it successfully overcame Rv3406-mediated resistance.

Tethering small molecules to a phage display library: Discovery of a selective bivalent inhibitor of protein kinase A

We report a noncovalent tethering methodology for the fragment-based selection of bivalent ligands targeting protein kinases. In this approach, a small-molecule warhead, staurosporine, directs a phage display cyclic peptide library to the active site of cAMP-dependent protein kinase (PKA), allowing for targeted library enrichment. A cyclic peptide discovered through this selection, when covalently attached to a staurosporine derivative, displayed a 90-fold increase in affinity for PKA. Moreover, the bivalent inhibitor was shown to be significantly more selective than the starting warhead when tested against a small panel of kinases. Thus our general methodology allows for covalent linkage of known small-molecule ligands to biological libraries for discovering potent bivalent inhibitors of biological targets. Copyright

Deamination of 2′,3′-O-isopropylideneadenosine-5′- carboxylic acid catalyzed by adenosine deaminase (ADA) and adenylate deaminase (AMPDA): Influence of substrate ionization on the activity of the enzymes

Adenosine deaminase (ADA) and adenylate deaminase (AMPDA) catalyze the deamination of 2′,3′-O-isopropylideneadenosine-5′-carboxylic acid to the corresponding inosine derivative and dependence of the rate of enzymatic reaction on the ionization degree of the substrate has been studied at different pH values. Copyright Taylor & Francis Group, LLC.

Monoclonal Antibodies for the Detection of a Specific Cyclic DNA Adduct Derived from ω-6 Polyunsaturated Fatty Acids

Lipid peroxidation of polyunsaturated fatty acids (PUFAs) is an endogenous source of α,β-unsaturated aldehydes that react with DNA producing a variety of cyclic adducts. The mutagenic cyclic adducts, specifically those derived from oxidation of ω-6 PUFAs, may contribute to the cancer promoting activities associated with ω-6 PUFAs. (E)-4-Hydroxy-2-nonenal (HNE) is a unique product of ω-6 PUFAs oxidation. HNE reacts with deoxyguanosine (dG) yielding mutagenic 1,N2-propanodeoxyguanosine adducts (HNE-dG). Earlier studies showed HNE can also be oxidized to its epoxide (EH), and EH can react with deoxyadenosine (dA) forming the well-studied ?dA and the substituted etheno adducts. Using a liquid chromatography-based tandem mass spectroscopic (LC-MS/MS) method, we previously reported the detection of EH-derived 7-(1′,2′-dihydroxyheptyl)-1,N6-ethenodeoxyadenosine (DHH?dA) as a novel endogenous background adduct in DNA from rodent and human tissues. The formation, repair, and mutagenicity of DHH?dA and its biological consequences in cells have not been investigated. To understand the roles of DHH?dA in carcinogenesis, it is important to develop an immuno-based assay to detect DHH?dA in cells and tissues. In this study we describe the development of monoclonal antibodies specifically against DHH?dA and its application to detect DHH?dA in human cells.

A METTL3 inhibitor for repairing corneal damage and its drug application

The present invention discloses a METTL3 inhibitor for repairing corneal damage and pharmaceutical application thereof, the METTL3 inhibitor is a compound shown in formula (I) or a tautomer thereof, a racemic, a racemate, an enantiomer and an diastereomer, or a mixture thereof or a pharmaceutically acceptable salt thereof. METTL3 inhibitors of the present invention for repairing corneal damage. The present invention provides a small molecule compound capable of inhibiting the activity of the METTL3 protein to play a role in repairing corneal damage and its pharmaceutical applications, specifically the application of organic small molecules based on the structure of the METTL3 protein and related drugs. Compounds disclosed in the present invention are a potent METTL3 inhibitor, the compound is capable of inhibiting the formation of m6A modifications very well. Experiments in the present invention can be concluded that the compounds disclosed in the present invention may play a good corneal repair effect by inhibiting the METTL3 protein.

Biomarkers for Carcinogenesis and Uses Thereof

Provided herein are methods of reducing the recurrence of liver cancer in a subject.

Investigation on 2′,3′- O-Substituted ATP Derivatives and Analogs as Novel P2X3 Receptor Antagonists

Antagonists of the purinergic P2X3 receptors represent promising drugs for the treatment of inflammation and pain. The ATP derivative 2′,3′-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP) has been described as a potent competitive inhibitor of this receptor. In th

A selective inhibitor of the UFM1-activating enzyme, UBA5

Protein conjugation with ubiquitin and ubiquitin-like small molecules, such as UFM1, is important for promoting cancer cell survival and proliferation. Herein, the development of the first selective micromolar inhibitor of the UBA5 E1 enzyme that initiates UFM1 protein conjugation is described. This organometallic inhibitor incorporates adenosine and zinc(II)cyclen within its core scaffold and inhibits UBA5 noncompetitively and selectively over other E1 enzymes and a panel of human kinases. Furthermore, this compound selectively impedes the cellular proliferation (above 50?μM) of cancer cells containing higher levels of UBA5. This inhibitor may be used to further probe the intracellular role of the UFM1 pathway in disease progression.