17902-23-7 Usage
Description
Tegafur is an orally bioavailable prodrug form of 5-fluorouracil (5-FU), a chemotherapy agent. It is a white crystalline powder with a melting point of 164-165℃, soluble in water, ethanol, and dimethylformamide, but insoluble in ether and benzene. Tegafur is odorless and has a bitter taste. It is converted to 5-FU in vivo enzymatically or by cytochrome P450 oxidation, making it an effective treatment for various types of cancer due to its high chemotherapy index and lower toxicity compared to 5-FU.
Uses
Used in Anticancer Applications:
Tegafur is used as an antineoplastic agent for its role in cancer treatment. After activation by the liver in vivo, it becomes 5-fluorouracil, which is effective against gastric cancer, colon cancer, colorectal cancer, pancreatic cancer, breast cancer, and lung cancer. It inhibits the proliferation of cancer cells, such as HT-29, BxPC-3, and Panc02, and reduces tumor growth in mouse xenograft models.
Used in Isotope Labelled Applications:
Isotope labelled Tegafur (T013900) is used as an antineoplastic, providing a means to track and study the distribution and metabolism of the drug within the body, which can be beneficial for research and development in cancer treatment.
Used in Combination Therapy:
Formulations containing tegafur, in combination with uracil, have been used in the treatment of cancer. This combination enhances the effectiveness of tegafur by modulating the activation and deactivation of 5-FU, leading to improved treatment outcomes for patients with various types of cancer.
Antineoplastic
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 lookchem of Tian Ye.
Production methods
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.
Originator
Futraful,Taiho,Japan,1974
Manufacturing Process
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.
Therapeutic Function
Antineoplastic
Biochem/physiol Actions
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.
Safety Profile
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.
Check Digit Verification of cas no
The CAS Registry Mumber 17902-23-7 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,7,9,0 and 2 respectively; the second part has 2 digits, 2 and 3 respectively.
Calculate Digit Verification of CAS Registry Number 17902-23:
(7*1)+(6*7)+(5*9)+(4*0)+(3*2)+(2*2)+(1*3)=107
107 % 10 = 7
So 17902-23-7 is a valid CAS Registry Number.
InChI:InChI=1/C8H9FN2O3/c9-5-4-11(6-2-1-3-14-6)8(13)10-7(5)12/h4,6H,1-3H2,(H,10,12,13)/t6-/m1/s1
17902-23-7Relevant articles and documents
Studies of antitumor agents. 1. Resolution of racemic 1-(tetrahydro-2-furanyl)-5-fluorouracil into the R and S isomers and examination of the biological activities of the isomers
Yasumoto,Moriyama,Unemi,Hashimoto,Suzue
, p. 1592 - 1594 (1977)
1-(Tetrahydro-2-furanyl)-5-fluorouracil (Thf-FU), which is named Ftorafur or FT-207 and is used clinically as an antitumor agent, was conveniently synthesized by condensation of the trimethylsilyl derivative of 5-fluorouracil with 2-acetoxytetrahydrofuran using NaI as a catalyst. This optically inactive Thf-FU was resolved into optically active (R) (+) and (S) (-) Thf-FU in high optical purity and excellent yield by formation of diastereoisomers with brucine. 13C NMR data were obtained on Thf-FU and related compounds and the antibacterial activities and in vivo antitumor activities of these isomers were tested. The degradations of these isomers to 5-fluorouracil by liver microsomes were also examined. No significant differences were found in any of these properties of these isomers.
Synthesis of Tegafur by the Alkylation of 5-Fluorouracil under the Lewis Acid and Metal Salt-Free Conditions
Zasada, Aleksandra,Mironiuk-Puchalska, Ewa,Koszytkowska-Stawińska, Mariola
, p. 885 - 889 (2017)
A novel protocol for preparation of tegafur (a prodrug of 5-fluorouracil) is reported. The process involves the 1,8-diazabicycloundec-7-ene-mediated alkylation of 5-fluorouracil with 2-acetoxytetrahydrofuran at 90 °C, followed by treatment of the prepurified mixture of the alkylation products with aqueous ethanol at 70 °C. The yield of the two-step process is 72%.
Preparation method of tegafur
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Paragraph 0030-0055, (2021/04/21)
The invention belongs to the technical field of medicinal chemistry, and particularly relates to a preparation method of tegafur. The method for preparing the tegafur comprises the step of reacting 5-fluorouracil and 2, 3-dihydrofuran under the irradiation of blue light through a catalyst and a photosensitizer to obtain the tegafur. Through photocatalysis, the activation energy of the reaction can be remarkably reduced, and the reaction temperature is reduced, so that the reaction conditions are simplified, the reaction time is greatly shortened, the atom utilization rate is increased, and the method is more suitable for industrial production.
Preparation method of antitumor drug tegafur
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Paragraph 0028-0063, (2020/01/25)
The invention provides a preparation method of tegafur. The method mainly comprises the following steps: at room temperature, reacting 5-fluorouracil with 2-benzoyloxy tetrahydrofuran under the actionof an inorganic base and a phase transfer catalyst to obtain tegafur. Compared with the prior art, the method has the advantages of simple and easily available raw materials, simple operation, mild reaction conditions, stable quality, high yield, no pollution to the environment and suitability for industrial production, the purity of the obtained product is as high as 99.7%, and the maximum single impurity content is less than 0.1%.
