Studies on Antitumor Agents. IV. Syntheses and Antitumor Activities of Compounds related to 1-(Tetrahydro-2-furanyl)-5-fluorouracil Metabolites

Abstract

A hydroxylated metabolite of 1-(tetrahydro-2-furanyl)-5-fluorouracil (FT), 1-(trans-3-hydroxytetrahydro-2-furanyl)-5-fluorouracil (trans-3′-OH-FT, VIII) and its isomer, 1-(cis-3-hydroxytetrahydro-2-furanyl)-5-fluorouracil (cis-3′-OH-FT, VI), were synthesized and isolated at high purity. As compounds related to FT metabolites, 2,3′-anhydro-1-(cis-3-hydroxytetrahydro-2-furanyl)-5-fluorouracil (2,3′-anhydro-FT, V), 1-(2,5-dihydro-2-furanyl)-5-fluorouracil (3′,4′-dehydro-FT, XII) and 1-(5-acetoxytetrahydro-2-furanyl)-5-fluorouracil (5′-AcO-FT, XI) were also synthesized. The antitumor activities of these compounds against sarcoma 180 and L 1210 were examined. The activities of cis-3′-OH-FT (VI) and 2,3′-anhydro-FT (V) were found to be lower than that of FT. The activity of 5′-AcO-FT (XI) was the same as that of FT. 3′,4′-Dehydro-FT (XII) showed much greater activity than FT. © 1982, The Pharmaceutical Society of Japan. All rights reserved.