Tegafur

• Ftorafur
• (RS )-5 -fluoro-1 -(tetrahydro -2-furyl ) uracil
• (± )-5 -fluoro-1 -(tetrahydro -2-furyl ) uracil
• DL -5 -fluoro-1 -(tetrahydro -2-furyl ) uracil
• Rac -5 -fluoro-1 -(tetrahydro -2-furyl ) uracil

L01BC03

Cytostatic

Risk

• 930 mg · kg -1 ( LD50, rat, oral)
• 685 mg · kg -1 ( LD50, rat, i.v.)
• 775 mg · kg -1 ( LD50, mouse, oral)
• 685 mg · kg -1 ( LD50, mouse, i.v.)
• 34 mg · kg -1 ( LD50, dog, oral)

Template: Infobox chemical / molecular formula search available

Tegafur ( INN) is a drug which is mainly used as a cytostatic in chemotherapy of metastatic cancer of the stomach, colon and breast cancer. The drug belongs to the group of nucleoside analogues. In the liver, it is converted into 5-fluorouracil ( 5-FU), and is thus a prodrug that can be administered, in contrast to 5-FU orally.

Tegafur is given in combination with uracil, with which the compound is a 1:1 adduct. The uracil inhibits while the 5 -FU - degrading enzyme dihydropyrimidine dehydrogenase (DPD ).

Stereoisomerism

Tegafur contains a stereogenic center and thus are chiral, there are two enantiomers, (R )-5 -fluoro-1 -(tetrahydro -2-furyl ) uracil, and the mirror image (S )-5 -fluoro-1 -(tetrahydro -2-furyl ) uracil. Drug tegafur is a racemate [ 1:1 mixture of (R )-5 -fluoro-1 -(tetrahydro -2-furyl ) uracil, and ( S )-5- fluoro-1- (tetrahydro- 2-furyl) -uracil ] used, though, the different pharmacodynamics of drug enantiomers - with rare exceptions - is known.

Synthesis

The synthesis of tegafur starts from 5-fluorouracil, which is silylated in the first step by means of hexamethyldisilazane in the amide. The introduction of the tetrahydrofuranyl group is carried out by the reaction with 2- Chlortetrahydrofuran. The target molecule is then obtained by removal of the trimethylsilyl group by means of methanolic ammonia solution. The reaction sequence results in the racemate.

Properties

Racemic tegafur occurs in four polymorphic forms. The α -, β - and δ - forms can be obtained by solvent crystallization. The γ - form is formed by transformation from the enantiotropic α - or β - form at 162 ° C and 120 ° C and melts at 175 ° C. The δ - form has a melting point at 165 ° C. For the α - and β - form crystal structures were examined by Röntgeneinkristalluntersuchungen. The α form is crystallized in a triclinic crystal lattice with space group P1. For the β - form of a monoclinic crystal lattice with the space group P21 / n was determined. Both forms form in the crystal lattice by hydrogen bonds linked dimers from. The difference is that in the α - form of a link via the NH- group and the carbonyl structure and the urea analog β - form takes place them via the NH- group and the carbonyl structure säureamidanaloge.