CAS 70-00-8|Trifluridine|Viroptic|Trifluorothymidine|5-Trifluorothymidine|trifluridine|1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dion...

General Information

Structure

Molecular Formula

C₁₀H₁₁F₃N₂O₅

Molecular Mass

296.1999496

Exact Mass

296.06200612

Charge

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

Canonic Smiles

OC[C@H]1O[C@H](C[C@@H]1O)n1cc(c(=O)[nH]c1=O)C(F)(F)F

Isomeric Smiles

FC(F)(F)c1cn([C@@H]2O[C@@H]([C@@H](O)C2)CO)c(=O)[nH]c1=O

Calculated Properties

JChem

Acid pKa

7.598577

H Acceptors

H Donor

LogD (pH = 5.5)

-0.75803435

LogD (pH = 7.4)

-0.9644963

Log P

-0.7546265

Molar Refractivity

56.3445

Polarizability

21.74243

Polar Surface Area

99.1

Rotatable Bonds

Lipinski's Rule of Five

true

ALOGPS 2.1

Log P

-0.45

LOG S

-1.65

Solubility (Water)

6.69e+00 g/l

Data Source

Names and Identifiers

Synonyms

TrifluridineViropticTrifluorothymidine5-TrifluorothymidineTrifluridineα,α,α-Trifluorothymidine2′-Deoxy-5-trifluoromethyluridineTrifluorothymine deoxyribosideTrifluorothymidine5-(Trifluoromethyl)-2'-deoxyuridine2'-Deoxy-5-(trifluoromethyl)uridineTrifluorothymidine

IUPAC Traditional name

trifluridine

IUPAC name

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

Brand Name

TrifluoromethyldeoxyuridineF3TDRTrifluorothymidineViroptictrifluorothymine deoxyribosideF3TTrifluridina [INN-Spanish]Trifluridinum [INN-Latin]TFTFluridineVirophtaF3DThdTrifluridine [USAN:INN]TFDU

Names and Identifiers

Registration numbers

MDL Number

MFCD00006534

PubChem SID

1609637782490002746506192

EC Number

200-722-8

PubChem CID

6256

CAS Number

70-00-8

Registration numbers

Properties

Product Information

95+%

≥99% (HPLC)

Free Base

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Properties

Related Proteins

No Data Available

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Molecular Spectra

No Data Available

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Molecule 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]

Molecule Details

References

PubChem Literature

From Data Sources

• 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

• 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

• www.bentham.org/prc/samples/prc1-1/Higashi.pdf

References

Bioactivity

PubChem BioAssay

Bioactivity

Names and Identifiers

Synonyms

IUPAC Traditional name

trifluridine

IUPAC name

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

Brand Name

TrifluoromethyldeoxyuridineF3TDRTrifluorothymidineViroptictrifluorothymine deoxyribosideF3TTrifluridina [INN-Spanish]Trifluridinum [INN-Latin]TFTFluridineVirophtaF3DThdTrifluridine [USAN:INN]TFDU

Registration numbers

MDL Number

MFCD00006534

PubChem SID

1609637782490002746506192

EC Number

200-722-8

PubChem CID

6256

CAS Number

70-00-8

References

PubChem Literature

From Data Sources

• 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

• 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

• www.bentham.org/prc/samples/prc1-1/Higashi.pdf

Bioactivity

PubChem BioAssay

Properties

Product Information

95+%

≥99% (HPLC)

Free Base

Download link

Molecule Details

DrugBank

DB00432

Drug Groups

approved

Description

Indication

Ophthalmic solution for the treatment of primay keratoconjunctivitis and recurrent epithelial keratitis due to herpes simplex virus, types 1 and 2.

Pharmacology

Toxicity

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]

External Links

• [Wikipedia]

• [RxList]

• [Drugs.com]

Molecule

ID:315