Antitumor activity of 1-alkoxycarbonylalkylcarbamoyl-5-fluorouracil derivatives by oral administration.
Antitumor activity of seven 5-fluorouracil derivatives having carbamoyl linkage with amino acid was examined against L-1210 leukemia, adenocarcinoma 755, ascites sarcoma 180, Ehrlich ascites carcinoma and Lewis lung carcinoma by oral administration. These compounds showed more than 30% increase in life-span (ILS) against L-1210 at optimal doses when given by oral administration. Therapeutic ratios (ILSmax/ILS30) of 1-methoxycarbonylmethylcarbamoyl and 1-(1-ethoxycarbonyl-3-methylthiopropylcarbamoyl) derivatives of 5-fluorouracil in L-1210 system were 4.8 and 4.7, respectively. 1-Methoxycarbonylmethylcarbamoyl and 1-(2-ethoxycarbonylethylcarbamoyl) derivatives of 5-fluorouracil inhibited completely the growth of adenocarcinoma 755 when given orally, but only 1-methoxycarbonylmethylcarbamoyl derivative inhibited 99 and 98% of the growth of ascites sarcoma 180 and Ehrlich ascites carcinoma, respectively. The latter compound increased the life-span to 48% at optimal dose in Lewis lung carcinoma system.
D000230:Adenocarcinoma / Q000188:drug therapy; D000284:Administration, Oral; D000818:Animals; D000970:Antineoplastic Agents; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D007939:Leukemia L1210 / Q000188:drug therapy; D008175:Lung Neoplasms / Q000188:drug therapy; D008297:Male; D051379:Mice; D009374:Neoplasms, Experimental / Q000188:drug therapy*; D012510:Sarcoma 180 / Q000188:drug therapy
D000970:Antineoplastic Agents; D005472:Fluorouracil