Antineoplastic agents. 2. Structure-activity studies on N-protected vinyl, 1,2-dibromoethyl, and cyanomethyl esters of several amino acids

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Abstract
Previously reported work on N-protected activated esters of phenylalanine was extended to include N-protected vinyl, dibromoethyl and cyanomethyl esters of several other amino acids. These compounds were synthesized and evaluated in mouse Ehrlich ascites carcinoma, rat Walker 256 carcinosarcoma and P388 lymphocytic leukemia tests. Among compounds tested were derivatives of tyrosine, tryptophan, glycine, leucine, proline, aspartic acid, glutamic acid, 4-aminobutyric acid and 6-aminocaproic acid. Compounds of greatest potential interest from this study are N-carbobenzoxyglycine-1,2-dibromoethyl ester and N-carbobenzoxy-L-leucine-1,2-dibromoethyl ester. Both compounds were highly active in Ehrlich ascites test systems (33 mg/kg per day). The glycine derivative was also active in the Walker 256 test (2.5 mg/kg per day). Values for LD50 in mice were 148 mg/kg (0.37 mmol/kg) and 225 mg/kg (0.50 mmol/kg) for glycine and leucine derivatives, respectively. These compounds do not appear to be toxic at effective dose levels.
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