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Oteracil

Oteracil structure

CAS No:
937-13-3
Formula:
C4H3N3O4
Chemical Name:
Oteracil
Synonyms:
1,3,5-Triazine-2-carboxylic acid,1,4,5,6-tetrahydro-4,6-dioxo-;Allantoxanic acid;1,4,5,6-Tetrahydro-4,6-dioxo-1,3,5-triazine-2-carboxylic acid;5-Azaorotic acid;s-Triazine-2,4-dione-6-carboxylic acid;2,4-Dioxo-1,2,3,4-tetrahydro-1,3,5-triazine-6-carboxylic acid;Oxonic acid;Oteracil;499-10-5
Categories:
Pharmaceutical Intermediates > Bulk Drug Intermediates

Description

5-azaorotic acid is a member of 1,3,5-triazines and a monocarboxylic acid.|Oteracil is an adjunct to antineoplastic therapy, used to reduce the toxic side effects associated with chemotherapy. Approved by the European Medicines Agency (EMA) in March 2011, Oteracil is available in combination with [DB09257] and [DB09256] within the commercially available product "Teysuno". The main active ingredient in Teysuno is [DB09256], a pro-drug of [DB00544] (5-FU), which is a cytotoxic anti-metabolite drug that acts on rapidly dividing cancer cells. By mimicking a class of compounds called "pyrimidines" that are essential components of RNA and DNA, 5-FU is able to insert itself into strands of DNA and RNA, thereby halting the replication process necessary for continued cancer growth. Oteracil's main role within Teysuno is to reduce the activity of 5-FU within normal gastrointestinal mucosa, and therefore reduce's gastrointestinal toxicity. It functions by blocking the enzyme orotate phosphoribosyltransferase (OPRT), which is involved in the production of 5-FU.|Oteracil is a modulator of 5-fluorouracil (5-FU) activity and inhibitor of the enzyme orotate phosphoribosyl-transferase (OPRT), with chemoprotective activity. Oteracil preferentially localizes in the gastrointestinal (GI) tract where it inhibits OPRT, thereby decreasing metabolism of 5-FU into its active metabolite 5-fluorouridine-5'-monophosphate (FUMP). This decreases activated 5-FU-related gastrointestinal toxicity.|Antagonist of urate oxidase.

Oteracil Basic Attributes

Molecular Weight：

157.08400

Exact Mass：

157.08

UNII：

5VT6420TIG

DSSTox ID：

DTXSID9048358

NCI Thesaurus Code：

C76917

ATC Code：

L01BC53

HScode：

2933699090

Characteristics

PSA：

116.17000

XLogP3：

-1

Density：

2.19g/cm3

Melting Point：

261-262 °C (decomp)

Boiling Point：

771.4ºC at 760mmHg

Flash Point：

420.4ºC

Toxicity

Protein Binding：

Oteracil, gimeracil, 5-FU, and tegafur are 8.4%, 32.2%, 18.4%, and 52.3% protein bound, respectively.

Drug Information

Drug Indication：

Oteracil is used as an adjunct to antineoplastic therapy. When used within the product Teysuno, oteracil is indicated for the treatment of adults with advanced gastric (stomach) cancer when given in combination with cisplatin.|Teysuno is indicated in adults for the treatment of advanced gastric cancer when given in combination with cisplatin.

Absorption：

After administration of a single dose of 50 mg Teysuno (expressed as tegafur content), median Tmax for Teysuno components tegafur, gimeracil, and oteracil was 0.5, 1.0, and 2.0 hours, respectively.|Following a single dose of Teysuno, approximately 3.8% to 4.2% of administered tegafur, 65% to 72% of administered gimeracil, and 3.5% to 3.9% of administered oteracil were excreted unchanged in the urine.|Although no intravenous data are available for Teysuno in humans, the volume of distribution could be roughly estimated from the apparent volume of distribution and urinary excretion data as 16 l/m2, 17 l/m2, and 23 l/m2 for tegafur, gimeracil and oteracil, respectively.

Metabolism/Metabolites：

Based on the results of in vitro studies, a part of oteracil is non-enzymatically degraded to 5-azauracil (5-AZU) by gastric fluid, and is then converted to cyanuric acid (CA) in the digestive tract. Only a small amount of oteracil is metabolised in the liver because of its low permeability.

Biological Half-Life：

Following a single dose of Teysuno, T1/2 values ranged from 6.7 to 11.3 hours for tegafur, from 3.1 to 4.1 hours for gimeracil, and from 1.8 to 9.5 hours for oteracil.

Mechanism of Action：

Oteracil's main role within Teysuno is to reduce the activity of 5-FU within normal gastrointestinal mucosa, and therefore reduce's gastrointestinal toxicity. It functions by blocking the enzyme orotate phosphoribosyltransferase (OPRT), which is involved in the production of 5-FU.

MeSH Entry Terms：

Oteracil

Oteracil Use and Manufacturing

Use Classification：

Human drugs -> Teysuno -> EMA Drug Category|Antineoplastic agents -> Human pharmacotherapeutic group

Computed Properties

Molecular Weight:157.08
XLogP3:-1
Hydrogen Bond Donor Count:3
Hydrogen Bond Acceptor Count:4
Rotatable Bond Count:1
Exact Mass:157.01235559
Monoisotopic Mass:157.01235559
Topological Polar Surface Area:108
Heavy Atom Count:11
Complexity:269
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes