2',3',5'-Tri-O-acetyluridine Chemical Properties

Melting point:

127.0 to 131.0 °C

Density 

1.43±0.1 g/cm3(Predicted)

storage temp. 

Inert atmosphere,Store in freezer, under -20°C

solubility 

Chloroform (Slightly), Dichloromethane (Slightly), DMSO (Slightly)

form 

Solid

pka

9.39±0.10(Predicted)

color 

Off-White

InChI

InChI=1S/C15H18N2O9/c1-7(18)23-6-10-12(24-8(2)19)13(25-9(3)20)14(26-10)17-5-4-11(21)16-15(17)22/h4-5,10,12-14H,6H2,1-3H3,(H,16,21,22)/t10-,12-,13-,14-/m1/s1

InChIKey

AUFUWRKPQLGTGF-QRMSVCKNSA-N

SMILES

C(OC(=O)C)[C@H]1O[C@@H](N2C=CC(=O)NC2=O)[C@H](OC(=O)C)[C@@H]1OC(=O)C

CAS DataBase Reference

4105-38-8(CAS DataBase Reference)

Safety Information

Safety Statements 

24/25

WGK Germany 

3

HS Code 

29349990

MSDS

• Language:English Provider:SigmaAldrich

2',3',5'-Tri-O-acetyluridine Usage And Synthesis

Description

Uridine triacetate is an orally available pro-drug of uridine approved by the FDA for the treatment of the rare autosomal recessive disorder called hereditary orotic aciduria. The drug was also approved for treating overdose of two chemotherapies (fluorouracil and capecitabine). Uridine triacetate was developed by Wellstat Therapeutics and licensed to BTG.

Chemical Properties

White or almost white crystalline powder

Uses

2’,3’,5’-Triacetyluridine is used in the treatment of Alzheimer’s disease in mice and provide neuroprotective effects. Shown to also decrease depressive symptoms and increases in brain pH bipolar patients.

Definition

ChEBI: Uridine triacetate is an acetate ester that is uracil in which the three hydroxy hydrogens are replaced by acetate group. A prodrug for uridine, it is used for the treatment of hereditary orotic aciduria and for management of fluorouracil toxicity. It has a role as a prodrug, a neuroprotective agent and an orphan drug. It is a member of uridines and an acetate ester.

Synthesis

Commercially available uridine (167) was treated with acetic anhydride in the presence of catalytic boron trifluoride-etherate, and the crude product was recrystallized from ethanol to give uridine triacetate (XX) in 74-78% yield.

Research

Administration of 200 mg/kg of 5-fluorouracil (FUra) to mice bearing human colon carcinoma DLD-1 xenografts resulted in 100% mortality. Oral administration of 2000 mg/kg of 2‘,3’,5‘-tri-O-acetyluridine (TAU), a prodrug of uridine, in combination with 120 mg/kg of 5-(benzyloxy benzyl)barbituric acid acyclonucleoside (BBBA), the most potent known inhibitor of uridine phosphorylase (UrdPase, EC 2.4.2.3), 2 hr after the administration of the same dose of FUra completely protected the mice (100% survival) from the toxicity of FUra. This combination also reduced tumor weight by 67% compared with 46% achieved by the maximum tolerated dose (50 mg/kg) of FUra alone. Similarly, administration of BBBA plus TAU 1 hr before or 4 hr after the administration of FUra reduced the tumor weight by 53 and 37%, respectively. TAU alone did not protect from FUra host toxicity. The efficiency of the BBBA plus TAU combination in rescuing from FUra host toxicities is attributed to the exceptional effectiveness of this combination in raising and maintaining higher plasma uridine concentrations than those achieved by TAU alone or by equimolar doses of uridine. The present results suggest that the BBBA plus TAU combination can provide a better substitute for the massive doses of uridine required to achieve the high levels of uridine necessary to rescue or protect from FUra host toxicities without the toxic side-effects associated with such doses of uridine[2].

References

[1] E.D. Gudio, M.L. Ferreira, L.E. Iglesias . “A rational approach to the regioselective deacetylation of 2′,3′,5′-tri-O-acetyluridine by Novozym 435 catalysed alcoholysis.” Biochimica et biophysica acta. Proteins and proteomics 1824 4 (2012): Pages 627-636.
[2] Osama M Ashour . “Modulation of 5-fluorouracil host toxicity by 5-(benzyloxybenzyl)barbituric acid acyclonucleoside, a uridine phosphorylase inhibitor, and 2′,3′,5′-tri-O-acetyluridine, a prodrug of uridine.” Biochemical pharmacology 60 3 (2000): Pages 427-431.

2',3',5'-Tri-O-acetyluridine(4105-38-8)Related Product Information

• 1-beta-D-Arabinofuranosyluracil
• Doxifluridine
• Floxuridine
• Sodium triacetoxyborohydride
• Trifluridine
• 2',3',5'-Triacetylguanosine
• uridine diphosphate glucose {= UDP-glucose}
• 2',3',5'-TRI-O-BENZOYLURIDINE
• Diethyleneglycol diformate
• 2'-Deoxyuridine
• 2'-O-Methyluridine
• (2-ISOPROPOXYETHYL) ACETATE
• TETRAHYDROFURFURYL ACETATE
• Uridine
• Diethyleneglycol diacetate
• Uracil
• 3'-DEOXYURIDINE
• 1-amino-3-methoxy-propan-2-ol