Studies on Antitumor Agents. VI. Syntheses and Antitumor Activities of Acyl Derivatives of 2'-Deoxy-5-trifluoromethyluridine

抄録

Various O-acyl and N-acyl derivatives of 2'-deoxy-5-trifluoromethyluridine (F₃Thd) were synthesized; namely 5'-O-acyl, 3', 5'-di-O-acyl, N³-acyl, 3', 5'-di-O-acetyl-N³-acyl, 3', 5'-di-O-carbamoyl and 3', 5'-di-O-ethoxycarbonyl compounds. 5'-O-Acyl derivatives of 2'-deoxy-5-trifluoromethylcytidine were also synthesized.
The antitumor activities of these compounds against sarcoma 180 were examined by oral administration to mice. Among the 5'-and 3', 5'-diester compounds with aliphatic acids, the 5'-O-hexanoyl compound showed the highest activity. Full protection of the sugar moiety with aroyl or carbamoyl groups considerably decreased the activities, and those of the 3', 5'-di-O-m-fluorobenzoyl and 3, 5'-di-O-butylcarbamoyl compounds were the smallest. N³-Benzoyl compounds were slightly more effective than F₃Thd but none of them showed higher activity than the effective O-acyl compounds. In the case of 5'-O-acylates of 2'-deoxy-5-trifluoromethylcytidine, the 5'-O-benzoyl compound showed the highest activity.