Synthesis and biological activity of O-alkyl-3-N-aminoacyloxymethyl-5-fluoro-2'-deoxyuridine derivatives.
In an attempt to improve the effectiveness of action of 5-fluoro-2'-deoxyuridine (FUdR), various kinds of O-alkylated water-soluble analogues were synthesized. Antitumor activities against sarcoma 180 (solid) were also evaluated. Some compounds exhibited potent activities. In particular, 3'-O-p-chlorobenzyl-3-N-aminoacyloxy-methylester derivatives were effective over a very wide range of dose and gave extremely large therapeutic ratios compared with known 5-fluorouracil (5-FU) derivations.
Harada
N
N
Lead Optimization Research Laboratory, Tanabe Seiyaku Co., Ltd., Saitama, Japan.
Hongu
M
M
Kawaguchi
T
T
Ohohashi
M
M
Oda
K
K
Hashiyama
T
T
Tsujihara
K
K
D000818:Animals; D000964:Antimetabolites, Antineoplastic / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D003857:Deoxyuridine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D005260:Female; D005467:Floxuridine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D051379:Mice; D008813:Mice, Inbred ICR; D012510:Sarcoma 180 / Q000188:drug therapy
D000964:Antimetabolites, Antineoplastic; D005467:Floxuridine; D003857:Deoxyuridine