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Triacetyluridine
Also known as: 4105-38-8, 2',3',5'-tri-o-acetyluridine, Triacetyluridine, Vistonuridine, Pn401, 2',3',5'-triacetyluridine
Molecular Formula
C15H18N2O9
Molecular Weight
370.31  g/mol
InChI Key
AUFUWRKPQLGTGF-FMKGYKFTSA-N
FDA UNII
2WP61F175M

Uridine Triacetate is a synthetic uridine pro-drug that is converted to uridine in vivo. Uridine, a pyrimidine nucleotide, has been used in a variety of diseases including depressive disorders and inherited myopathies. (NCI04)
1 2D Structure

Triacetyluridine

2 Identification
2.1 Computed Descriptors
2.1.1 IUPAC Name
[(2R,3R,4R,5R)-3,4-diacetyloxy-5-(2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl acetate
2.1.2 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
2.1.3 InChI Key
AUFUWRKPQLGTGF-FMKGYKFTSA-N
2.1.4 Canonical SMILES
CC(=O)OCC1C(C(C(O1)N2C=CC(=O)NC2=O)OC(=O)C)OC(=O)C
2.1.5 Isomeric SMILES
CC(=O)OC[C@@H]1[C@H]([C@H]([C@@H](O1)N2C=CC(=O)NC2=O)OC(=O)C)OC(=O)C
2.2 Other Identifiers
2.2.1 UNII
2WP61F175M
2.3 Synonyms
2.3.1 MeSH Synonyms

1. 2',3',5'-tri-o-acetyluridine

2. Pn 401

3. Pn-401

4. Pn401

5. Rg-2133

6. Rg2133

7. Triacetyluridine

8. Xuriden

2.3.2 Depositor-Supplied Synonyms

1. 4105-38-8

2. 2',3',5'-tri-o-acetyluridine

3. Triacetyluridine

4. Vistonuridine

5. Pn401

6. 2',3',5'-triacetyluridine

7. Xuriden

8. Tri-o-acetyluridine

9. Uridine 2',3',5'-triacetate

10. Vistogard

11. (2r,3r,4r,5r)-2-(acetoxymethyl)-5-(2,4-dioxo-3,4-dihydropyrimidin-1(2h)-yl)tetrahydrofuran-3,4-diyl Diacetate

12. Triacetyl Uridine

13. Uridine, 2',3',5'-triacetate

14. Pn 401

15. Pn-401

16. Rg2133

17. Rg 2133

18. Rg-2133

19. Mfcd00023795

20. 2wp61f175m

21. Unii-2wp61f175m

22. Uridinetriacetate

23. Uridine Triacetate [usan:inn]

24. Uridine-triacetate

25. Vistogard (tn)

26. Einecs 223-881-5

27. Xuriden (tn)

28. Uridine, 2,3,5-triacetate

29. Mls006009982

30. Schembl871011

31. Uridine Triacetate [mi]

32. Chembl2107381

33. Uridine Triacetate (usan/inn)

34. Uridine Triacetate [inn]

35. Chebi:90914

36. Dtxsid40961409

37. Uridine Triacetate [usan]

38. [(2r,3r,4r,5s)-3,4-diacetyloxy-5-(2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl Acetate

39. Cs-d1799

40. Uridine Triacetate [who-dd]

41. Zinc3843198

42. Nsc788948

43. S6484

44. Akos015964563

45. Db09144

46. Nsc-788948

47. [(2r,3r,4r,5r)-3,4-diacetyloxy-5-(2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methyl Acetate

48. Uridine Triacetate [orange Book]

49. Hy-14905

50. Smr004701034

51. Sy004945

52. 2',3',5'-tri-o-acetyluridine, >=98%

53. D09985

54. 105t388

55. A825419

56. J-700012

57. Q22075857

58. Uridine 2',3',5'-triacetate;2',3',5'-triacetyluridine

59. 2 Inverted Exclamation Mark ,3 Inverted Exclamation Mark ,5 Inverted Exclamation Mark -triacetyluridine

2.4 Create Date
2005-08-08
3 Chemical and Physical Properties
Molecular Weight 370.31 g/mol
Molecular Formula C15H18N2O9
XLogP3-0.5
Hydrogen Bond Donor Count1
Hydrogen Bond Acceptor Count9
Rotatable Bond Count8
Exact Mass370.10123016 g/mol
Monoisotopic Mass370.10123016 g/mol
Topological Polar Surface Area138 Ų
Heavy Atom Count26
Formal Charge0
Complexity660
Isotope Atom Count0
Defined Atom Stereocenter Count4
Undefined Atom Stereocenter Count0
Defined Bond Stereocenter Count0
Undefined Bond Stereocenter Count0
Covalently Bonded Unit Count1
4 Drug and Medication Information
4.1 Drug Indication

Marketed as the product Xuriden (FDA), uridine triacetate is indicated for the treatment of hereditary orotic aciduria. Marketed as the product Vistogard (FDA), uridine triacetate is indicated for the emergency treatment of adult and pediatric patients in the following situations: following a fluorouracil or capecitabine overdose regardless of the presence of symptoms; or who exhibit early-onset, severe or life-threatening toxicity affecting the cardiac or central nervous system, and/or early-onset, unusually severe adverse reactions (e.g., gastrointestinal toxicity and/or neutropenia) within 96 hours following the end of fluorouracil or capecitabine administration.


FDA Label


5 Pharmacology and Biochemistry
5.1 FDA Pharmacological Classification
5.1.1 Pharmacological Classes
Pyrimidine Analog [EPC]; Pyrimidines [Chemical/Ingredient]; Analogs/Derivatives [Chemical/Ingredient]
5.2 ATC Code

A - Alimentary tract and metabolism

A16 - Other alimentary tract and metabolism products

A16A - Other alimentary tract and metabolism products

A16AX - Various alimentary tract and metabolism products

A16AX13 - Uridine triacetate


5.3 Absorption, Distribution and Excretion

Absorption

Maximum concentrations of uridine in plasma following oral administration are generally achieved within 2 to 3 hours.


Route of Elimination

Uridine can be excreted via the kidneys, but is also metabolized by normal pyrimidine catabolic pathways present in most tissues.


Volume of Distribution

Circulating uridine is taken up into mammalian cells via specific nucleoside transporters, and also crosses the blood brain barrier.


5.4 Metabolism/Metabolites

Following oral administration, uridine triacetate is deacetylated by nonspecific esterases present throughout the body, yielding uridine in the circulation.


5.5 Biological Half-Life

2 to 2.5 hours


5.6 Mechanism of Action

Uridine triacetate is a synthetic uridine pro-drug that is converted to uridine in vivo. When used for the treatment or prevention of toxicity associated with fluorouracil and other antimetabolites, uridine triacetate is utilized for its ability to compete with 5-fluorouracil (5-FU) metabolites for incorporation into the genetic material of non-cancerous cells. It reduces toxicity and cell-death associated with two cytotoxic intermediates: 5-fluoro-2'-deoxyuridine-5'-monophosphate (FdUMP) and 5-fluorouridine triphosphate (FUTP). By pre-administering with uridine (as the prodrug uridine triacetate), higher doses of 5-FU can be given allowing for improved efficacy and a reduction in toxic side effects such as neutropenia, mucositis, diarrhea, and handfoot syndrome. Uridine triacetate is also used for replacement therapy in the treatment of hereditary orotic aciduria, also known as uridine monophosphate synthase (UMPS) deficiency. As a result of UMPS deficiency, patients experience a systemic deficiency of pyrimidine nucleotides, accounting for most symptoms of the disease. Additionally, orotic acid from the de novo pyrimidine pathway that cannot be converted to UMP is excreted in the urine, accounting for the common name of the disorder, orotic aciduria. Furthermore, orotic acid crystals in the urine can cause episodes of obstructive uropathy. When administered as the prodrug uridine triacetate, uridine can be used by essentially all cells to make uridine nucleotides, which compensates for the genetic deficiency in synthesis in patients with hereditary orotic aciduria.


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