ANTITUMOR ACTIVITY OF 1-ALKOXYCARBONYLALKYLCAR-BAMOYL-5-FLUOROURACIL DERIVATIVES BY ORAL ADMINISTRATION

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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 (ILS_max/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.