In the hope to find antitumor candidates among di-(2-chloroethyl)sulfides it was found that only 3-chloro-4-(2-chloroethylthio)butanoic (3-chloro) and 4-chloro-3-(2-chloroethylthio)butanoic (4-chloro) acids possess definite alkylating ability which is suggested to be a reason of their high antitumor activity. However, the clinical use of these agents is hampered by their high toxicity. A number of arylamides and cyclohexylamides of 3-chloro and 4-chloro acids were synthesized. A study of the toxicity and antitumor activity of synthesized derivatives in comparison with known 4-chloro-3-(2-chloroethylthio)butanoic acids shows that both 3-chloro and 4-chloro isomers possess high antitumor activity. Substitution of 3-chloro and 4-chloro butanoic acids by arylamides and cyclohexylamides residues R did not appear to increase the antitumor activity of the compounds. The presence of an anilide and cyclohexylamides carboxylic or alkylenecarboxylic substituent reduced the toxicity of the compounds 3-5 times in comparison with 3-chloro and 4-chloro anilides and cyclohexylamides. All synthesized compounds possess a broad spectrum of antitumor activity and are less toxic than the parent compound 4-chloro-3-(2-chloroethylthio)butanoic acid.
Amides Animals