Tegafur is a anticancer drug.it is a fluorouracil derivative, in vitro it has no anti-tumor effect, after it goes into the human body ,by the role of the liver drug metabolism enzymes and microsomal enzymes P-450 in the liver, its tetrahydrofuran ring is taken off, fluorouracil (5-FU)is gradually released to produce cytotoxicity. Variety of tumor inhibition is similar to 5-FU, its mechanism of inhibition is inhibiting thymidine synthetase, blocking deoxy thymidylate converting to pyrimidine nucleotide, thereby interfering and blocking the synthesis of DNA, RNA and protein .
Tegafur index of chemotherapy is twice of 5-FU and toxicity is 1/6~1/5 of 5-FU ,there is cross-resistance between 5-FU and the product,it belongs to cycle-specific drugs, tegafur belongs to the time-dependent cytostatic, preferable absorption after oral , Tmax is 2h, it slowly releases 5-FU in vivo, blood level is not very high, it can maintain a longer time, so it has a low toxicity in vivo.the Intravenous infusion is better than the one-time injection. After the drug going into the body, it is evenly distributed in the liver, small intestine, spleen, lung, kidney and brain, liver and kidney having the highest concentrations. T1/2 is 5~18.6h. Inhibition of DNA, RNA synthesis can maintain 12~20h. After 24h, the content of each tissue is significantly reduced. It is Mainly excreted in the urine and respiratory tract , within 24h after administration, 23% is by the urine excretion of the prototype , 55% is excreted from the respiratory tract in the form of CO2. This product is highly fat-soluble, widely distributed, easily through the blood-brain barrier, its cerebrospinal fluid concentration is higher than 5-FU.
This product is effective against a variety of solid tumors, it is primarily used for the treatment of digestive system cancers, tegafur has a effective rate of 30% to 33% on gastric cancer ,it has a certain effect on colon cancer, colorectal cancer, lung cancer, primary and metastatic liver cancer, pancreatic cancer , cholangiocarcinoma, gallbladder cancer, prostate cancer, kidney cancer, bladder cancer . It can also be used to treat breast cancer, head and neck squamous cell carcinoma, lung cancer and liver cancer. It is Also used as a radiation sensitizer before and after surgery treatment to prevent cancer recurrence, proliferation and metastasis. Overall, the efficacy of this product is a little better than 5-FU.
The above information is edited by the Chemicalbook of Tian Ye.
White crystalline powder. Melting point 164-165 ℃, soluble in water, ethanol, dimethylformamide, insoluble in ether, benzene. Odorless, bitter taste.
this product is a derivative of 5-fluorouracil, the role and application of the product is the same as 5-fluorouracil, but it has less toxicity and its chemotherapy index is high. After the activion by the liver in vivo ,it becomes 5-fluorouracil to play a role in cancer. It is effective on Gastric cancer, colon cancer, colorectal cancer, pancreatic cancer and breast cancer, lung cancer.
After condensatio from 5-fluorouracil and 2-acetoxy tetrahydrofurann, the product is obtained. The yield rate of this method is only15%. Another method is using 5-fluorouracil, hexamethyl silazane and trimethylchlorosilane as starting materials to produce tegafur.
Tegafur is an orally bioavailable prodrug form of 5-fluorouracil (5-FU; ). It is converted to 5-FU in vivo enzymatically or by cytochrome P450 oxidation. Tegafur inhibits proliferation of HT-29, BxPC-3, and Panc02 cells (IC50s = 201, 172, and 179 μM, respectively). It also reduces tumor growth in an HT-27 colon carcinoma mouse xenograft model when administered at a dose of 50 mg/kg and in a 4-1ST gastric carcinoma mouse xenograft model when used in combination with uracil. Formulations containing tegafur, in combination with uracil, have been used in the treatment of cancer.
Futraful,Taiho,Japan,1974
Isotope labelled Tegafur (T013900), used as an antineoplastic.
ChEBI: Tegafur is an organohalogen compound and a member of pyrimidines.
One process from US Patent 4,107,162: 27.4 g of 2,4-bis(trimethylsilyl)-5-
fluorouracil and 7.7 g of 2,3-dihydrofuran are dissolved in 70 ml of
acetonitrile, and 30 ml of an acetonitrile solution containing 1.3 g of
anhydrous stannic chloride are added thereinto with cooling and stirring. 50
ml of acetonitrile containing 1.3 ml of water dissolved therein are then
dropwise added over 15 minutes. After return to room temperature, the
reaction is further effected with stirring at 40°C for 5 hours. The reaction
mixture is neutralized by adding 1 N aqueous ammonia with cooling and stirring (conversion 83%). After the nondissolved substances are removed by
filtration, the filtrate is concentrated and dried under reduced pressure. 100
ml of water and 300 ml of dichloromethane are added to the residue to
completely dissolve the residue by stirring. The obtained dichloromethane
layer is separated. The water layer is subjected to extraction twice with
dichloromethane. The thus obtained extracts are combined with the separated
dichloromethane layer and the combined extracts, after drying with anhydrous
magnesium sulfate, are concentrated and dried. The obtained residue is
dissolved in ethanol, and the nondissolved substances are removed by
filtration. The filtrate is subjected to recrystallization to give white crystals,
followed by further recrystallization of the mother liquor. There are totally
obtained 15.6 g of N1-(2'-furanidyl)-5-fluorouracil.Yield: 78% of theory, with
respect to 2,4-bis(trimethylsilyl)-5-fluorouracil.
An alternative process from US Patent 3,635,946: A vigorously stirred reaction
mixture consisting of 32.87 g (0.1 mol) of 5-fluorouracilmercury, 100 ml of
dimethylformamide and 50 ml of toluene is dried by azeotropic distillation of
toluene. It is then cooled to -40°C in a stream of dry nitrogen, and a solution
of 21.3 g (0.2 mol) of 2-chlorofuranidin in 20 ml of dried dimethylformamide
is gradually added to the stirred mixture, the temperature being maintained
between -40°C and -30°C. After completion of the reaction (which is marked
by complete dissolution of the starting 5-fluorouracilmercury) i.e. after about
3 to 4 hours, 60 to 80 ml of the solvent are distilled off in vacuo at a bath
temperature not exceeding 35°C. 50 to 70 ml of dry acetone are then added
and also vacuum distilled. The residue is easily crystallized. It is collected,
washed three times with small quantities of ethanol - 10 ml each - and airdried.
12.2 g of N1-(2'-furanidyl)-5-fluorouracil are obtained in the form of
white crystalline solids; melting point 160°C to 162°C. Additional treatment of
the mother liquor yields 3.0 g more of the product. Yield: 75% of theory,
based on the starting 5-fluorouracilmercury.
After recrystallization from ethanol, 14.3 g of N1-(2'-furanidyl)-5-
fluorouracilare obtained, MP 164°C to 165°C.
Tegafur is a pro-drug of 5-fluorouracil, an antimetabolite used as an antineoplastic agent. It has been used as adjuvant chemotherapy for curatively resected colorectal cancer therapy.
Poison by ingestion.
Moderately toxic to humans by intravenous
route. Moderately toxic experimentally by
intraperitoneal, intravenous, and
subcutaneous routes. Experimental
teratogenic data. Human systemic effects:
nausea and vomiting. Experimental
reproductive effects. Questionable human
carcinogen producing gastrointestinal
tumors. Human mutation data reported.
Used as an anti-cancer agent. When heated
to decomposition it emits very toxic fumes
of Fand NOx.
[1] Y M EL SAYED W S. Metabolic activation of R,S-1-(tetrahydro-2-furanyl)-5-fluorouracil (ftorafur) to 5-fluorouracil by soluble enzymes.[J]. Cancer research, 1983, 43 9: 4039-4044.
[2] DIKLA ENGEL. Novel Prodrugs of Tegafur that Display Improved Anticancer Activity and Antiangiogenic Properties[J]. Journal of Medicinal Chemistry, 2007, 51 2: 314-323. DOI:
10.1021/jm7009827[3] MITSUHARU HANADA Takashi Y Toshihiro Noguchi. Amrubicin, a novel 9-aminoanthracycline, enhances the antitumor activity of chemotherapeutic agents against human cancer cells in vitro and in vivo[J]. Cancer Science, 2007, 98 3: 447-454. DOI:
10.1111/j.1349-7006.2007.00404.x
