- 著者
- JUN-ICHI YAMASHITA SETSUO TAKEDA HIROSHI MATSUMOTO TADAFUMI TERADA NORIO UNEMI MITSUGI YASUMOTO
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.35, no.5, pp.2090-2094, 1987-05-25 (Released:2009-10-19)
- 参考文献数
- 14
- 被引用文献数
- 6 6
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.
- 著者
- JUN-ICHI YAMASHITA SETSUO TAKEDA HIROSHI MATSUMOTO NORIO UNEMI MITSUGI YASUMOTO
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.35, no.6, pp.2373-2381, 1987-06-25 (Released:2009-10-19)
- 参考文献数
- 12
- 被引用文献数
- 3 3
Various O-alkoxyalkyl derivatives of 2'-deoxy-5-trifluoromethyluridine (F3Thd) were synthesized, and the antitumor activities of the compounds against sarcoma 180 were examined by oral administration to mice. Among the formal-type derivatives, 3', 5'-di-O-ethoxymethyl (3), 3', 5'-di-O-benzyloxymethyl (12), 5'-O-benzyloxymethyl (13) and 3'-O-benzyloxymethyl (14) compounds showed high activities, which were six-fold higher than that of F3Thd itself. Since acetal-type derivatives were unstable under acidic conditions, antitumor testing of the compounds was also carried out with co-administration of sodium bicarbonate. 5'-O- (1-Ethoxypropyl) -F3Thd (25) and 5'-O- (1-benzyloxypropyl) -F3Thd (37) showed the highest activities among the acetal-type derivatives, but the ED50 values of the compounds were not lower than those of effective formal-type compounds.These O-alkoxyalkyl derivatives of F3Thd are resistant to degradation by thymidine phosphorylase and are activated by microsomal drug-metabolizing enzymes after absorption.