1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione

• ChemBase ID: 315
• Molecular Formular: C10H11F3N2O5
• Molecular Mass: 296.1999496
• Monoisotopic Mass: 296.06200612
• SMILES: FC(F)(F)c1cn([C@@H]2O[C@@H]([C@@H](O)C2)CO)c(=O)[nH]c1=O
• Canonical SMILES: OC[C@H]1O[C@H](C[C@@H]1O)n1cc(c(=O)[nH]c1=O)C(F)(F)F
• InChI: InChI=1S/C10H11F3N2O5/c11-10(12,13)4-2-15(9(19)14-8(4)18)7-1-5(17)6(3-16)20-7/h2,5-7,16-17H,1,3H2,(H,14,18,19)/t5-,6+,7+/m0/s1
• InChIKey: VSQQQLOSPVPRAZ-RRKCRQDMSA-N

NAMES AND DATABASE IDS

Names

• IUPAC name: 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione
• IUPAC Traditional name: trifluridine
• Brand Name: F3DThd; F3T; F3TDR; Fluridine; TFDU; TFT; Trifluoromethyldeoxyuridine; Trifluorothymidine; Trifluridina [INN-Spanish]; Trifluridine [USAN:INN]; Trifluridinum [INN-Latin]; Virophta; Viroptic; trifluorothymine deoxyriboside
• Synonyms: α,α,α-Trifluorothymidine; 2′-Deoxy-5-trifluoromethyluridine; Trifluorothymine deoxyriboside; Trifluridine; Trifluorothymidine; Trifluridine; Viroptic; Trifluorothymidine; 5-Trifluorothymidine; 2'-Deoxy-5-(trifluoromethyl)uridine; 5-(Trifluoromethyl)-2'-deoxyuridine; Trifluorothymidine

Database IDs

• CAS Number: 70-00-8
• EC Number: 200-722-8
• MDL Number: MFCD00006534
• PubChem SID: 46506192; 160963778; 24900027
• PubChem CID: 6256

CALCULATED PROPERTIES

JChem

• Acid pKa: 7.598577
• H Acceptors: 5
• H Donor: 3
• LogD (pH = 5.5): -0.75803435
• LogD (pH = 7.4): -0.9644963
• Log P: -0.7546265
• Molar Refractivity: 56.3445 cm^3
• Polarizability: 21.74243 Å^3
• Polar Surface Area: 99.1 Å^2
• Rotatable Bonds: 3
• Lipinski's Rule of Five: true

ALOGPS 2.1

• Log P: -0.45
• LOG S: -1.65
• Solubility (Water): 6.69e+00 g/l

PROPERTIES

Physical Property

• Solubility: 1560 mg/L; DMSO; Methanol
• Apperance: White to Off-White Solid
• Melting Point: 175-178°C; 190-193 °C(lit.)
• Hydrophobicity(logP): -0.7

Safety Information

• Storage Condition: -20°C; Refrigerator
• Storage Warning: IRRITANT
• RTECS: XP2087500
• European Hazard Symbols: Harmful (Xn)
• German water hazard class: 3
• Risk Statements: 20/21/22-40
• Safety Statements: 22-36
• TSCA Listed: false
• GHS Pictograms: GHS07; GHS08
• GHS Signal Word: Warning
• GHS Hazard statements: H302-H312-H332-H351
• GHS Precautionary statements: P280
• Personal Protective Equipment: dust mask type N95 (US), Eyeshields, Gloves
• Storage Temperature: -20°C

Product Information

• Purity: ≥99% (HPLC); 95+%
• Salt Data: Free Base

DETAILS

DrugBank - DB00432

• Drug Groups: approved
• Description: An antiviral derivative of thymidine used mainly in the treatment of primary keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus. (From Martindale, The Extra Pharmacopoeia, 30th ed, p557)
• Indication: Ophthalmic solution for the treatment of primay keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus, types 1 and 2.
• Pharmacology: Trifluridine is a fluorinated pyrimidine nucleoside with in vitro and in vivo activity against herpes simplex virus, types 1 and 2 and vacciniavirus. Some strains of adenovirus are also inhibited in vitro. Trifluridine is also effective in the treatment of epithelial keratitis that has not responded clinically to the topical administration of idoxuridine or when ocular toxicity or hypersensitivity to idoxuridine has occurred. In a smaller number of patients found to be resistant to topical vidarabine, trifluridine was also effective. Trifluridine interferes with DNA synthesis in cultured mammalian cells. However, its antiviral mechanism of action is not completely known.
• Toxicity: Overdosage by ocular instillation is unlikely because any excess solution should be quickly expelled from the conjunctival sac. Acute overdosage by accidental oral ingestion has not occurred. However, should such ingestion occur, the 75 mg dosage of trifluridine in a 7.5 mL bottle of trifluridine is not likely to produce adverse effects. Single intravenous doses of 1.5 to 30 mg/kg/day in children and adults with neoplastic disease produce reversible bone marrow depression as the only potentially serious toxic effect and only after three to five courses of therapy. The acute oral LD₅₀ in the mouse and rat was 4379 mg/kg or higher.
• Affected Organisms: Human Herpes Virus
• Biotransformation: One major metabolite, 5-carboxy-2'-deoxyuridine found on the endothelial side of the cornea, indicating localized metabolism.
• Absorption: Systemic absorption of trifluridine following therapeutic dosing with trifluridine ophthalmic appears to be negligible.
• Half Life: Approximately 12 to 18 minutes following ophthalmic administration.
• References: Costin D, Dogaru M, Popa AS, Cijevschi I: [Trifluridine therapy in herpetic in keratitis] Rev Med Chir Soc Med Nat Iasi. 2004 Apr-Jun;108(2):409-12. [Pubmed] ; Kuster P, Taravella M, Gelinas M, Stepp P: Delivery of trifluridine to human cornea and aqueous using collagen shields. CLAO J. 1998 Apr;24(2):122-4. [Pubmed] ; O'Brien WJ, Taylor JL: Therapeutic response of herpes simplex virus-induced corneal edema to trifluridine in combination with immunosuppressive agents. Invest Ophthalmol Vis Sci. 1991 Aug;32(9):2455-61. [Pubmed] ; Overman MJ, Kopetz S, Varadhachary G, Fukushima M, Kuwata K, Mita A, Wolff RA, Hoff P, Xiong H, Abbruzzese JL: Phase I clinical study of three times a day oral administration of TAS-102 in patients with solid tumors. Cancer Invest. 2008 Oct;26(8):794-9. [Pubmed] ; Hong DS, Abbruzzese JL, Bogaard K, Lassere Y, Fukushima M, Mita A, Kuwata K, Hoff PM: Phase I study to determine the safety and pharmacokinetics of oral administration of TAS-102 in patients with solid tumors. Cancer. 2006 Sep 15;107(6):1383-90. [Pubmed] ; Temmink OH, Prins HJ, van Gelderop E, Peters GJ: The Hollow Fibre Assay as a model for in vivo pharmacodynamics of fluoropyrimidines in colon cancer cells. Br J Cancer. 2007 Jan 15;96(1):61-6. Epub 2006 Dec 19. [Pubmed]
• External Links: Wikipedia; RxList; Drugs.com

Selleck Chemicals - S1778

Research Area: Infection
Biological Activity:
Trifluridine(Viroptic) is an anti-herpesvirus antiviral drug, used primarily on the eye. It is a nucleoside analogue, a modified form of deoxyuridine, similar enough to be incorporated into viral DNA replication, but the -CF3 group added to the uracil component blocks base pairing. [1]

Sigma Aldrich - T2255

Application
Trifluorothymidine (Trifluridine, TFT) is a substrate used to study the specificity and kinetics of thymidine kinase(s). TFT after phosphorylation may be incorporated into DNA where is induces DNA-damage, consequently TFT is useful for studies of DNA repair mechanisms. TFT may also be used to study mechanisms of inhibition of thymidylate synthase(s).

REFERENCES

• Temmink OH, Prins HJ, van Gelderop E, Peters GJ: The Hollow Fibre Assay as a model for in vivo pharmacodynamics of fluoropyrimidines in colon cancer cells. Br J Cancer. 2007 Jan 15;96(1):61-6. Epub 2006 Dec 19. Pubmed
• Costin D, Dogaru M, Popa AS, Cijevschi I: [Trifluridine therapy in herpetic in keratitis] Rev Med Chir Soc Med Nat Iasi. 2004 Apr-Jun;108(2):409-12. Pubmed
• Kuster P, Taravella M, Gelinas M, Stepp P: Delivery of trifluridine to human cornea and aqueous using collagen shields. CLAO J. 1998 Apr;24(2):122-4. Pubmed
• O'Brien WJ, Taylor JL: Therapeutic response of herpes simplex virus-induced corneal edema to trifluridine in combination with immunosuppressive agents. Invest Ophthalmol Vis Sci. 1991 Aug;32(9):2455-61. Pubmed
• Overman MJ, Kopetz S, Varadhachary G, Fukushima M, Kuwata K, Mita A, Wolff RA, Hoff P, Xiong H, Abbruzzese JL: Phase I clinical study of three times a day oral administration of TAS-102 in patients with solid tumors. Cancer Invest. 2008 Oct;26(8):794-9. Pubmed
• Hong DS, Abbruzzese JL, Bogaard K, Lassere Y, Fukushima M, Mita A, Kuwata K, Hoff PM: Phase I study to determine the safety and pharmacokinetics of oral administration of TAS-102 in patients with solid tumors. Cancer. 2006 Sep 15;107(6):1383-90. Pubmed
• www.bentham.org/prc/samples/prc1-1/Higashi.pdf