Antitumor and antiinflammatory agents: N-benzoyl-protected cyanomethyl esters of amino acids.
A series of N-protected cyanomethyl esters of various amino acids was synthesized and tested for antineoplastic and antiinflammatory activity in rodents. Utilizing the L-phenylalanine cyanomethyl ester and varying the N-protecting moiety demonstrated that the N-tosyl and the N-Cbz analogues were the most active against Ehrlich ascites cell proliferation. The N-(carbobenzyloxy)- and N-benzoyl-L-phenylalanine cyanomethyl esters were the most active against carrageenan-induced inflammation. In the N-benzoyl series of cyanomethyl esters, L-alanine, DL-valine, and L-leucine amino acid analogues were the most active against Ehrlich ascites cell proliferation. The glycine and L-alanine analogues possessed the best inhibitor activity in the antiinflammatory screen. The cyanomethyl esters also demonstrated immunosuppressive activity and the ability to suppress the writhing reflex which is associated with inflammatory pain. However, no antipyretic or narcotic analgesic activity was demonstrated by these agents.
D000097:Acetonitriles / Q000138:chemical synthesis / Q000494:pharmacology; D000596:Amino Acids / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis*; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001831:Body Temperature / Q000187:drug effects; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D002351:Carrageenan; D004952:Esters; D007166:Immunosuppressive Agents / Q000138:chemical synthesis; D007928:Lethal Dose 50; D007941:Leukemia P388 / Q000188:drug therapy; D008297:Male; D051379:Mice; D008811:Mice, Inbred DBA; D051381:Rats; D011930:Reaction Time / Q000187:drug effects; D013329:Structure-Activity Relationship
D000097:Acetonitriles; D000596:Amino Acids; D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D004952:Esters; D007166:Immunosuppressive Agents; D002351:Carrageenan