STUDIES ON THE ANTITUMOR ACTIVITY OF 1, 3-BIS (TETRAHYDRO-2-FURANYL) -5-FLUORO-2, 4-PYRIMIDINEDIONE (FD-1), A NEW ANTITUMOR AGENT. I

ANTITUMOR ACTIVITY OF FD-1 BY THE ORAL ADMINISTRATION

Abstract

The antitumor activity of 1, 3-Bis (tetrahydro-2-furanyl) -5-fluoro-2, 4-pyrimidinedione (FD-1) was compared with that of 1- (2-Tetrahydrofuryl) -5-fluorouracil (FT) or 5-Fluorouracil (5-FU) in a number of tumor systems.
FD-1 had significant activity against the solid forms but not the ascitic forms, and it produced a greater inhibition in tumor growth than FT. On AH 130 solid form, the therapeutic index (LD₅₀/ED₅₀) of FD-1 and FT were respectively 18. 3 and 10.6.
FD-1 was evaluated against the ip and sc implanted L 1210 leukemia by single, intermittent or daily administration. FD-1 retained some degree of antileukemic activity against the ic implanted L 1210.
No significant difference in antitumor activity was observed between the R and S isomers or the racemic mixture (FD-1).
A higher activity of FD-1 compared to FT was possibly due to the increased 5-FU level in tumor through its metabolite, 3- (tetrahydro-2-furanyl) -5-fluoro-2, 4-pyrimidinedione (3-FT).