Studies on antitumor agents. 8. Antitumor activities of O-alkyl derivatives of 2'-deoxy-5-(trifluoromethyl)uridine and 2'-deoxy-5-fluorouridine

O-Benzyl and O-ethyl derivatives of 2'-deoxy-5-(trifluoromethyl)uridine (F3Thd) and 2'-deoxy-5-fluorouridine (FUdR) were synthesized. The oral antitumor activity of the compounds against sarcoma 180 in mice was examined. The 5'-O-ethyl (3b), 3'-O-ethyl (3c), 5'-O-benzyl (3e)...

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Published in:Journal of medicinal chemistry 1989-01, Vol.32 (1), p.136-139
Main Authors: Yamashita, Junichi, Yasumoto, Mitsugi, Takeda, Setsuo, Matsumoto, Hiroshi, Unemi, Norio
Format: Article
Language:English
Subjects:
Administration, Oral
Animals
Antineoplastic Agents - chemical synthesis
Chemical Phenomena
Chemistry
Exact sciences and technology
Floxuridine - analogs & derivatives
Floxuridine - chemical synthesis
Floxuridine - pharmacology
Heterocyclic compounds
Heterocyclic compounds with several n hetero atoms in the same ring, in separated rings or in fused rings
Male
Mice
Mice, Inbred ICR
Organic chemistry
Preparations and properties
Sarcoma 180 - drug therapy
Structure-Activity Relationship
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Summary:O-Benzyl and O-ethyl derivatives of 2'-deoxy-5-(trifluoromethyl)uridine (F3Thd) and 2'-deoxy-5-fluorouridine (FUdR) were synthesized. The oral antitumor activity of the compounds against sarcoma 180 in mice was examined. The 5'-O-ethyl (3b), 3'-O-ethyl (3c), 5'-O-benzyl (3e), and 3'-O-benzyl (3f) derivatives of F3Thd were 4-fold more active than F3Thd itself. Among the substituted-benzyl derivatives of F3Thd, 3'-O-(p-chlorobenzyl)-F3Thd (3h) showed the highest activity, with an ED50 less than one-tenth of that of F3Thd. The activities of 5'-O-benzyl (7c) and 3'-O-benzyl (7d) derivatives of FUdR were equal to those of the effective O-alkyl derivatives of F3Thd.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm00121a025