5-fluoro-1,2,3,4-tetrahydropyrimidine-2,4-dione

• ChemBase ID: 426
• Molecular Formular: C4H3FN2O2
• Molecular Mass: 130.0772232
• Monoisotopic Mass: 130.01785557
• SMILES: Fc1c(=O)[nH]c(=O)[nH]c1
• Canonical SMILES: Fc1c[nH]c(=O)[nH]c1=O
• InChI: InChI=1S/C4H3FN2O2/c5-2-1-6-4(9)7-3(2)8/h1H,(H2,6,7,8,9)
• InChIKey: GHASVSINZRGABV-UHFFFAOYSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 5-fluoro-1,2,3,4-tetrahydropyrimidine-2,4-dione
• IUPAC Traditional name: fluorouracil
• Brand Name: 5 Fluorouracil; Adrucil; Arumel; Carac; Carzonal; Effluderm; Efudex; Efudix; Efurix; FU; Fluoroblastin; Fluoroplex; Fluracil; Fluracilum; Fluri; Fluril; Fluro Uracil; Ftoruracil; Kecimeton; Phthoruracil; Phtoruracil; Queroplex; Timazin; URF; Ulup
• Synonyms: 5-Fluoro-2,4(1H,3H)pyrimidinedione; 5-Fluoropyrimidine-2,4-diol; Adrucil; Arumel; Flurablastin; Queroplex; Ro 2-9757; Timazin; U 8953; Ulup; 5-Fluoro Uracil; 5-fluoropyrimidine-2,4(1H,3H)-dione; Fluorouracil; 5-Fluorouracil; 2,4-Dihydroxy-5-fluoropyrimidine; 5-Fluoro-2,4(1H,3H)-pyrimidinedione; 5-Fluorouracil; Fluorouracil; 5-FU; Carac; Efudex; Fluoroplex; Adrucil(Fluorouracil); 5-Fluoropyrimidine-2,4(1H,3H)-dione; 5-Fluorouracil 99%; 5-Fluorouracil; 2,4-二羟基-5-氟嘧啶; 5-氟-2,4(1H,3H)-嘧啶二酮; 5-氟脲嘧啶; 5-氟尿嘧啶

Database IDs

• CAS Number: 51-21-8
• EC Number: 200-085-6
• MDL Number: MFCD00006018
• Beilstein Number: 127172
• Merck Index: 144181
• PubChem SID: 160963889; 46508557; 24888466; 24871165
• PubChem CID: 3385

CALCULATED PROPERTIES

JChem

• Acid pKa: 6.7786403
• H Acceptors: 2
• H Donor: 2
• LogD (pH = 5.5): -0.6778695
• LogD (pH = 7.4): -1.3501022
• Log P: -0.6558481
• Molar Refractivity: 26.1722 cm^3
• Polarizability: 9.588146 Å^3
• Polar Surface Area: 58.2 Å^2
• Rotatable Bonds: 0
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: -0.58
• LOG S: -1.35
• Solubility (Water): 5.86e+00 g/l

PROPERTIES

Physical Property

• Solubility: < 0.1 g/100 mL at 19 °C; DMSO; H2O: soluble10 mg/mL, clear; Water
• Apperance: off-white to white powder; White Solid
• Melting Point: 130.5 °C; 280-282°C(dec); 280-282°C; 282-286 °C (dec.); 282-286 °C (dec.)(lit.); 282-286(dec.)°C; ca 282°C dec.
• Boiling Point: 190-200°C/0.1mm
• Hydrophobicity(logP): -0.8

Safety Information

• Storage Condition: -20°C; Refrigerator; Room Temperature (15-30°C), Protect from light
• Storage Warning: IRRITANT, TOXIC, CORROSIVE; Light Sensitive; Toxic/Light Sensitive/Keep Cold
• RTECS: YR0350000
• European Hazard Symbols: Corrosive (C); Toxic (T); Harmful (Xn)
• UN Number: 2811; 2928; UN2811
• German water hazard class: 3
• Hazard Class: 6.1; 8
• Packing Group: 3; II; III
• Australian Hazchem: 2XE
• Risk Statements: 22; 61-22-48/22-68; R:22-34
• Safety Statements: 53-45; S:26-27/28-36/37/39-46-64
• EU Classification: TC2
• EU Hazard Identification Number: 6.1B
• Emergency Response Guidebook(ERG) Number: 154
• TSCA Listed: true; 是
• GHS Pictograms: GHS07; GHS08
• GHS Hazard statements: H360-H341-H373-H302
• GHS Precautionary statements: P260-P281-P301+P312-P308+P313-P405-P501A
• RID/ADR: UN 2811 6.1/PG 3

Pharmacology Properties

• Target: Antimetabolites

Product Information

• Purity: ~99%; ≥99.0% (HPLC); 97%; 98.5%; 98+%; 99%
• Salt Data: Free Base
• Empirical Formula (Hill Notation): C4H3FN2O2

DETAILS

MP Biomedicals - 02101722

Crystalline
Purity: ~99%

DrugBank - DB00544

• Drug Groups: approved
• Description: A pyrimidine analog that is an antineoplastic antimetabolite. It interferes with DNA synthesis by blocking the thymidylate synthetase conversion of deoxyuridylic acid to thymidylic acid. [PubChem]
• Indication: For the topical treatment of multiple actinic or solar keratoses. In the 5% strength it is also useful in the treatment of superficial basal cell carcinomas when conventional methods are impractical, such as with multiple lesions or difficult treatment sites. Fluorouracil injection is indicated in the palliative management of some types of cancer, including colon, esophageal, gastric, rectum, breast, biliary tract, stomach, head and neck, cervical, pancreas, renal cell, and carcinoid.
• Pharmacology: Fluorouracil is an antineoplastic anti-metabolite. Anti-metabolites masquerade as purine or pyrimidine - which become the building blocks of DNA. They prevent these substances from becoming incorporated into DNA during the "S" phase (of the cell cycle), stopping normal development and division. Fluorouracil blocks an enzyme which converts the cytosine nucleotide into the deoxy derivative. In addition, DNA synthesis is further inhibited because Fluorouracil blocks the incorporation of the thymidine nucleotide into the DNA strand.
• Toxicity: LD₅₀=230mg/kg (orally in mice)
• Affected Organisms: Humans and other mammals
• Biotransformation: Hepatic
• Absorption: 28-100%
• Half Life: 10-20 minutes
• Protein Binding: 8-12%
• Elimination: Seven percent to 20% of the parent drug is excreted unchanged in the urine in 6 hours; of this over 90% is excreted in the first hour.; The remaining percentage of the administered dose is metabolized, primarily in the liver.
• References: Longley DB, Harkin DP, Johnston PG: 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003 May;3(5):330-8. [Pubmed] ; Petty RD, Cassidy J: Novel fluoropyrimidines: improving the efficacy and tolerability of cytotoxic therapy. Curr Cancer Drug Targets. 2004 Mar;4(2):191-204. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Apollo Scientific Ltd - PC4380

Antineoplastic agent. Not USP. Not for drug use.

Selleck Chemicals - S1209

Research Area: Cancer
Biological Activity:
Fluorouracil (5-FU or f5U) is a chemotherapy drug that is a pyrimidine analog which is used in the treatment of cancer. It works through noncompetitive inhibition of thymidylate synthase. Due to its noncompetitive nature and effects on thymidine synthesis, 5-FU is frequently referred to as the "suicide inactivator". It belongs to the family of drugs called antimetabolites. It is typically administered with leucovorin. [1] Fluorouracil IC50 values were observed across the National Cancer Institute NCI60 panel of human tumor cell lines, which exhibit a mean IC50 of 17.6 μM, with a range of 1–501 μM. [2]

Sigma Aldrich - 858471

Packaging
5 g in glass bottle
Application
Inhibitor of DNA synthesis.1,2

Sigma Aldrich - 47576

Other Notes
Potent antineoplastic agent. Its determination in tissue with microbore HPLC and fluorescence detection1; Metabolised to fluoro-2′-deoxyuridine monophosphate which inhibits DNA synthesis by blocking thymidylate synthetase2

Toronto Research Chemicals - F596000

5-Fluoro Uracil is an active metabolite of Doxifluridine (D556750).

REFERENCES

• Longley DB, Harkin DP, Johnston PG: 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer. 2003 May;3(5):330-8. Pubmed
• Petty RD, Cassidy J: Novel fluoropyrimidines: improving the efficacy and tolerability of cytotoxic therapy. Curr Cancer Drug Targets. 2004 Mar;4(2):191-204. Pubmed
• http://en.wikipedia.org/wiki/Fluorouracil
• Bollag, W., et al.: Eur. J. Cancer, 16, 427 (1980)
• Pinedo, H., et al.: J. Clin. Oncol., 6, 1653 (1980)
• Ishikawa, T., et al.: Biochem. Pharmacol., 55, 1091 (1980)
• Schuller, J., et al.: Cancer Chemother. Pharmacol., 45, 291 (1980)
• Antineoplastic agent. Not for drug use.