著者

山下 純一 武田 節夫 松本 宏 寺田 忠史 采見 憲男 安本 三治

出版者

公益社団法人日本薬学会

雑誌

Chemical & pharmaceutical bulletin (ISSN:00092363)

巻号頁・発行日

vol.35, no.5, pp.2090-2094, 1987-05-25

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Various O-acyl and N-acyl derivatives of 2'-deoxy-5-trifluoromethyluridine (F_3Thd) were synthesized; namely 5'-O-acyl, 3',5'-di-O-acyl, N^3-acyl, 3',5'-di-O-acetyl-N^3-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. N^3-Benzoyl compounds were slightly more effective than F_3Thd but none of them showed higher activity than the effective O-acyl compounds. In the case of 5'-O-acylates of 2'-deoxy-5-trifluoroniethylcytidine, the 5'-O-benzoyl compound showed the highest activity.