16710-13-7

Basic information

• Product Name: NSC 112513
• Synonyms: NSC 112513;6-methyluridine;Uridine, 6-methyl-;1-((2R,3R,4S,5R)-3,4-Dihydroxy-5-(hydroxymethyl)tetrahydrofuran-2-yl)-6-methylpyrimidine-2,4(1H,3H)-dione
• CAS NO: 16710-13-7
• Molecular Formula: C₁₀H₁₄N₂O₆
• Molecular Weight: 258.228
• Mol File: 16710-13-7.mol

Chemical Properties

• Boiling Point: °Cat760mmHg
• Flash Point: °C
• Appearance: /
• Density: 1.576g/cm³
• Refractive Index: 1.618
• CAS DataBase Reference: NSC 112513(CAS DataBase Reference)
• NIST Chemistry Reference: NSC 112513(16710-13-7)
• EPA Substance Registry System: NSC 112513(16710-13-7)

Safety Data

• Hazardous Substances Data: 16710-13-7(Hazardous Substances Data)

Usage

Uses

Used in Pharmaceutical Industry:
NSC 112513 is used as a research compound for studying its potential antimalarial properties. It has demonstrated weak antimalarial activity against the P. falciparum 3D7 isolate, which is a strain of the Plasmodium falciparum parasite responsible for causing malaria in humans. This activity suggests that further research and development could lead to the enhancement of its efficacy as an antimalarial agent.
Additionally, NSC 112513 is used as a weak substrate for Escherichia coli pyrimidine nucleoside phosphorylase. This application is valuable in biochemical and enzymatic studies, as it helps researchers understand the enzyme's substrate specificity and its role in metabolic pathways. The use of NSC 112513 in this context contributes to the broader understanding of nucleoside metabolism and the development of potential therapeutic agents targeting these pathways.

InChI:InChI=1/C10H14N2O6/c1-4-2-6(14)11-10(17)12(4)9-8(16)7(15)5(3-13)18-9/h2,5,7-9,13,15-16H,3H2,1H3,(H,11,14,17)

Upstream product

• 107-71-1 tert-butyl peroxyacetate 
• 58-96-8 uridine 
• 16710-12-6 6-methyl-cytidine 
• 64898-15-3 2',3',5'-tris-O-(tert-butyldimethylsilyl)uridine 
• 74-88-4 methyl iodide 
• 23316-76-9 6-methyl-1-(2,3,5-tri-O-benzoyl-β-D-ribofuranosyl)-2,4(1H,3H)-pyrimidinedione 
• 25691-86-5 1β-D-ribofuranosyl-3-benzyl-6-methyluracil 
• 6974-32-9 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose 
• 638-13-1 6-methyl-4-sulfanylidene-1,2,3,4-tetrahydropyrimidin-2-one 
• 25589-18-8 3-benzyl-6-methylpyrimidine-2,4(1H,3H)-dione 
• 869880-87-5 5-bromo-5'-O-(tert-butyldimethylsilyl)-2',3'-O-isopropylidene uridine 
• 869880-90-0 6-cyano-5'-O-(tert-butyldimethylsilyl)-2',3'-O-isopropylidene uridine 
• 36807-62-2 1-(2',3',5'-tri-O-acetyl-β-D-ribofuranosyl)-6-methyluracil 
• 626-48-2 6-Methyluracil 

Downstream Products

• 626-48-2 6-Methyluracil 
• 50-69-1 D-ribose 
• 169886-81-1 5'-O-4,4'-dimethoxytrityl-6-methyluridine 
• 169886-85-5 5'-O-4,4'-dimethoxytrityl-2'-O-tert-butyldimethylsilyl-6-methyluridine 

Relevant articles and documents

Structure-activity relationships of C6-uridine derivatives targeting Plasmodia orotidine monophosphate decarboxylase

Malaria, caused by Plasmodia parasites, has re-emerged as a major problem, imposing its fatal effects on human health, especially due to multidrug resistance. In Plasmodia, orotidine 5′-monophosphate decarboxylase (ODCase) is an essential enzyme for the de novo synthesis of uridine 5′-monophosphate. Impairing ODCase in these pathogens is a promising strategy to develop novel classes of therapeutics. Encouraged by our recent discovery that 6-iodo uridine is a potent inhibitor of P. falciparum, we investigated the structure-activity relationships of various C6 derivatives of UMP. 6-Cyano, 6-azido, 6-amino, 6-methyl, 6-N-methylamino, and 6-N,N-dimethylamino derivatives of uridine were evaluated against P. falciparum. The mononucleotides of 6-cyano, 6-azido, 6-amino, and 6-methyl uridine derivatives were studied as inhibitors of plasmodial ODCase. 6-Azidouridine 5′-monophosphate is a potent covalent inhibitor of P. falciparum ODCase. 6-Methyluridine exhibited weak antimalarial activity against P. falciparum 3D7 isolate. 6-N-Methylamino and 6-N,N-dimethylamino uridine derivatives exhibited moderate antimalarial activities.

NMR-based conformational analysis of 2′,6-disubstituted uridines and antiviral evaluation of new phosphoramidate prodrugs

Six novel phosphoramidate prodrugs of uridine analogues, with structural modifications introduced at the 6- and 2′,6-positions, have been prepared and evaluated for selective antiviral activity against hepatitis C virus, as well as other positive-stranded RNA viruses. An analysis of the conformational properties of the parent nucleosides was carried out using two-dimensional NMR spectroscopy based experiments, highlighting a 3′-endo (North) sugar puckering preference and syn orientation.

Synthesis of 6-alkyluridines from 6-cyanouridine via zinc(II) chloride-catalyzed nucleophilic substitution with alkyl grignard reagents

6-Cyanouracil derivatives underwent a direct nucleophilic substitution reaction with alkyl Grignard reagents in the presence of zinc(II) chloride as a catalyst to form the corresponding 6-alkyluracils. This methodology is applicable to sugar-protected 6-cyanouridine and 6-cyano-2′-deoxyuridine without the protection at the N3-imide and provides a facile and general access to versatile 6-alkyluracil and 6-alkyluridine derivatives.

PYRIMIDINE DERIVATIVES AS ANTICANCER AGENTS

The present invention includes methods of treating or preventing cancer by administering an effective amount of 6-substituted pyrimidine derivatives of the Formula I to a subject need thereof:

Stereoselective synthesis of N1-6-methyluridine and related 2-substituted analogues

Coupling reaction of 2-substituted-6-methyl-4(3H)-pyrimidinones (1a,b) with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D-ribofuranose (ABR) afforded the corresponding N1-2,6-disubstituted nucleosides (2a,b) without any trace of the N3-isomer.

ODCASE INHIBITORS FOR THE TREATMENT OF MALARIA

The present invention includes methods of treating or preventing malaria by administering an anti-malarial effective amount of 6-substituted uridine derivatives to a subject need thereof. The invention also includes new 6-substituted uridine derivatives for use as therapeutics, in particular to treat malaria.

6-Substituted and 5,6-disubstituted derivatives of uridine: Stereoselective synthesis, interaction with uridine phosphorylase, and in vitro antitumor activity

Stereoselective procedures are described for the synthesis of 6- alkyluridines by Lewis acid-catalyzed condensation of (a) trimethylsilylated 6-alkyl-4-alkylthiouracils with 1-O-acetyl-2,3,5-tri-O-benzoyl-β-D- ribofuranose (ABR) and (b) trimethylsilylated 6-alkyl-3-benzyluracils with ABR. The 4-methylthio group was subsequently removed with the use of 1 N trifluoroacetic acid and the 3-benzyl group by a new modified procedure with the use of the complex BBr3-THF. Furthermore, 6-(hydroxymethyl)uridine (39) and 5-fluoro-6-(hydroxymethyl)uridine (40) were obtained by sequential oxidation with SeO2 and reduction with tetrabutylammonium borohydride of the 6-methyl group of 6-methyluridine (5) and 5-fluoro-6-methyluridine (35), and their corresponding 6-fluoromethyl congeners 41 and 42 were obtained by DAST treatment of 39 and 40, respectively. For all the foregoing nucleosides in the fixed syn conformation about the glycosyl bond, 1H NMR spectroscopy further demonstrated that the pentose rings exist predominantly in the conformation N (3'-endo). Most of the nucleosides were weak substrates of Escherichia coli pyrimidine nucleoside phosphorylase. Enhanced susceptibility to phosphorolysis was exhibited by two of them, 39 and 41, with 6-CH2OH and 6-CH2F substituents capable of formation of an additional hydrogen bond with the enzyme. The 5-fluoro-6-substituted uridines were the poorest substrates. Cytotoxicities of the nucleosides were examined vs the human tumor cell lines MOLT-3, U-937, K-562, and IM-9, as well as PHA-stimulated human lymphocytes. Two of the analogues, 5-fluoro-6-(fluoromethyl)uridine (42) and 5-fluoro-6- (hydroxymethyl)uridine (40), exhibited cytotoxicities comparable to that of 5-fluorouracil.

Synthesis of 6-aza- and 6-methyl-pyrimidine ribonucleoside phosphoramidites and their incorporation in hammerhead ribozymes

The synthesis of phosphoramidites of 6-modified pyrimidine ribonucleosides and their incorporation into hammerhead ribozymes and influence on nuclease stability and catalytic activity is described.

A SIMPLE AND GENERAL ENTRY TO 5-SUBSTITUTED URUDINES BASED ON THE REGIOSELECTIVE LITHIATHION CONTROLLED BY A PROTECTING GROUP IN THE SUGAR MOIETY

Lithiathion of 2',3',5'-tris-O-(tert-butyldimethylsilyl)uridine with sec-BuLi/TMEDA occurs at the C-5 position with a high regioselectivity and subsequent reactions of the resulting C-5 lithiated species with a variety of electrophiles provides a general entry to 5-substituted uridines.

Reactions of pyrimidine nucleosides with aqueous alkalies: kinetics and mechanisms.

Kinetics for the reactions of various cytosine and uracil nucleosides and their alkyl derivatives with aqueous sodium hydroxide have been studied by liquid chromatography. Blocking of the glycosyl hydroxyl groups with alkyl groups and changes in the glycon moiety configuration have been observed to exert only moderate effects on the rate of deamination of cytosine nucleosides. Methylation of the 4-amino group retards deamination considerably, while a methyl substituent at C5 is rate accelerating and at C6 only moderately rate retarding. These findings have been accounted for by a mechanism involving a rate limiting bimolecular displacement of the 4-amino group by a hydroxide ion. Analogous comparisons with uracil nucleosides suggest that the decomposition of uridine is initiated by an intermolecular attack of hydroxide ion on the C5 atom of the base moiety. In contrast, beta-D-arabino- and beta-D-lyxo-furanosyl derivatives appear to be cleaved via an intramolecular nucleophilic attack of the ionized 2'-hydroxyl group.