Synthesis of N-(Alkyl-N'-nitrosocarbamoyl)-amino Acid Ester Derivatives and their Anticancer Activity

N-(Alkyl-N'-nitrosocarbamoyl)-amino Acid Ester류의 合成 및 抗癌 作用 評價

The derivatives of N-(alkylcarbamoyl) amino acid methyl ester, N-(2-chloroethylcarbamoyl)-glycine methyl ester (7a), -valine methyl ester (8a), -phenylalanine methyl ester (9a), N-(N'-methylcarbamoyl)-glycine methyl ester (7b), -valine methyl ester (8b), and-phenylalanine methyl ester (9b), were prepared by reacting the corresponding free amino acid methyl ester (glycine-, valine-, phenylalanine-methyl ester) with isocyanate (R-N=C=O${\cdot};R=Cl-CH_2-CH_2-or\; CH_3-)$. The prepared N-(alkylcarbamoyl) amino acid methyl esters (7,8,9) were treated with $NaNO_2$/98% HCOOH in order to obtain their nitrosoated products, N-(alkyl-N'-nitrosocarbmoyl)amino acid methyl ester. The compound (7,8,9) gave N-(2-chloroethyl-N'-nitrosocarbamoyl)-valine methyl ester (14a),-phenylalanine methyl ester (15a), N-(N'-alkyl-N'-nitrosocarbamoyl)-glycine methyl ester (13b),-valine methyl ester. (14b), and-phenylalanine methyl ester (15b) respectively under the nitrosoation. On the other hand, N-(2-chloroethylcarbamoyl) glycine methyl ester produced N-(2-chloroethylcarbamoyl)-N-nitrosoglycine methyl ester (13a). The inhibitory activity of the prepared N-(alkylcarbamoyl) amino acid methyl ester (7,8,9) and N-(alkyl-N'-nitrosocarbamoyl) amino acid methyl ester (13,14,15) towards the growth of L1210 murine leukemia cells were examined. Among them the compound (14a) and (15a) exhibit excellent activity having $ED_{50}\; to\;be\;1.5{\mu}g/ml\;and\;3.0{\mu}g/ml respectively.