title: Antitumor agents: diazomethyl ketone and chloromethyl ketone analogues prepared from N-tosyl amino acids.
abstract: Diazomethyl ketone and chloromethyl ketone analogues prepared from N-tosyl amino acids have been synthesized and tested for antitumor activity in Ehrlich ascites carcinoma and P-388 lymphocytic leukemia screens in mice. The N-tosyl chloromethyl ketone analogues prepared from glycine, L-alanine, beta-alanine, L-valine, and 6-(N-tosyl-amino)caproic acid were the most potent antineoplastic agents in the Ehrlich ascites carcinoma screen. The N-tosyl diazomethyl ketone analogues synthesized from glycine, L-leucine, and L-proline were the most active of this series in the Ehrlich ascites screen, along with 5-keto-1-tosyl-2-(diazoacetyl)pyrrolidine and the diazomethyl ketone analogues prepared from 6-(N-tosylamino)caproic acid. In the P-388 lymphocytic leukemia screen, the N-tosyl chloromethyl ketone prepared from glycine and the compound 5-keto-1-tosyl-2-(diazoacetyl)pyrrolidine were the most active.
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D003978:Diazomethane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D007659:Ketones / Q000138:chemical synthesis* / Q000494:pharmacology; D007941:Leukemia P388 / Q000188:drug therapy; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D013329:Structure-Activity Relationship; D014105:Tosyl Compounds / Q000138:chemical synthesis / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D007659:Ketones; D014105:Tosyl Compounds; C015795:diazomethyl ketones; D003978:Diazomethane