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

• ChemBase编号: 315
• 分子式: C10H11F3N2O5
• 平均质量: 296.1999496
• 单一同位素质量: 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

名称和登记号

名称

• IUPAC标准名: 1-[(2R,4S,5R)-4-hydroxy-5-(hydroxymethyl)oxolan-2-yl]-5-(trifluoromethyl)-1,2,3,4-tetrahydropyrimidine-2,4-dione
• IUPAC传统名: trifluridine
• 商标名: F3DThd; F3T; F3TDR; Fluridine; TFDU; TFT; Trifluoromethyldeoxyuridine; Trifluorothymidine; Trifluridina [INN-Spanish]; Trifluridine [USAN:INN]; Trifluridinum [INN-Latin]; Virophta; Viroptic; trifluorothymine deoxyriboside
• 别名: 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

登记号

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

理论计算性质

JChem

• Acid pKa: 7.598577
• 质子受体: 5
• 质子供体: 3
• LogD (pH = 5.5): -0.75803435
• LogD (pH = 7.4): -0.9644963
• Log P: -0.7546265
• 摩尔折射率: 56.3445 cm^3
• 极化性: 21.74243 Å^3
• 极化表面积: 99.1 Å^2
• 可自由旋转的化学键: 3
• 里宾斯基五规则: true

ALOGPS 2.1

• Log P: -0.45
• LOG S: -1.65
• 溶解度: 6.69e+00 g/l

分子性质

理化性质

• 溶解度: 1560 mg/L; DMSO; Methanol
• 外观: White to Off-White Solid
• 熔点: 175-178°C; 190-193 °C(lit.)
• 疏水性(logP): -0.7

安全信息

• 保存条件: -20°C; Refrigerator
• 保存注意事项: IRRITANT
• RTECS编号: XP2087500
• 欧盟危险性物质标志: 有害性(Harmful) (Xn)
• 德国WGK号: 3
• 危险公开号: 20/21/22-40
• 安全公开号: 22-36
• TSCA收录: false
• GHS危险品标识: GHS07; GHS08
• GHS警示词: Warning
• GHS危险声明: H302-H312-H332-H351
• GHS警示性声明: P280
• 个人保护装置: dust mask type N95 (US), Eyeshields, Gloves
• 保存温度: -20°C

产品相关信息

• 纯度: ≥99% (HPLC); 95+%
• 成盐信息: Free Base

详细说明

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).

参考文献

• 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