Synthesis and antitumor activities of 5′-O-aminoacyl-3′-O-benzyl derivatives of 2′-deoxy-5-fluorouridine and related compounds

Article abstract of DOI:10.1248/cpb.44.150

Various O-alkyl derivatives of 2′-deoxy-5-fluorouridine (FUdR) were synthesized and their antitumor activities in mice bearing sarcoma 180 (s.c.-p.o.) were evaluated in terms of the ED₅₀ values (mg/kg/d). Most of these compounds were superior to FUdR in antitumor activity. In particular, the antitumor activity of 3′-O-(p-chlorobenzyl)-FUdR (3e) (ED₅₀ = 0.87 mg/kg/d) was as much as 100 times that of FUdR (ED₅₀ = 84 mg/kg/d). Further, various 5′-O-aminoacyl derivatives of 3e were synthesized and evaluated in terms of ED₅₀ value and therapeutic index (T.I.). Both the ED₅₀ value (0.41 mg/kg/d) and the T.I. (4.18) of 3′-O-(p-chlorobenzyl)-5′-O-glycyl-FUdR hydrochloride (6a) were significantly improved, compared with those of 3e and FUdR. FUdR plasma concentration after a single p.o. dosing of 6a was maintained for as long as 24 h.

Full text of DOI:10.1248/cpb.44.150

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