STUDIES ON A NTITUMOR CHEMOTHERAPEUTIC AGENTS——Ⅱ. SYNTHESIS OF CANTHARIDINE DERIVATIVES AND ANALOGUES

The preceeding paper of this series described the antitumor activity of cantharidinimide. In order to study the structure-activity relationship and further search for antitumor agent with higher activity and lower toxicity, a series of compounds with various structural modification was carried out. Eighty one derivatives of cantharidine with the following types Ⅰ, Ⅱ, Ⅲ, Ⅳ, Ⅴ were synthesized. The compounds prepared were listed in tables 1～5.Compounds 1-20 were obtained by condensation of cis-7-oxabicyclo(2,2,1) heptane-2,3-dicarboxylic anhydride with different amines in alcohol.Compounds 21-40 were carried out by condensation of bicyclo (2,2,1) heptane-2,3-dicarboxylic anhydride with pertinent amines in water or alcohol.Compounds 41-59 were prepared by condensation of desoxycantharidinimide with aliphatic amines or aromatic amines.Compounds 60-67 were synthesized by condensation of cantharidine with different amines.Compounds 68-81 were carried out by condensation of dimethylmaleic anhydride with pertinent amines in variant organic solvents.Preliminary result of animal screening showed compound 66 to be effective against mouse sarcoma 180 (ascites). Other compounds did not show any significant activity.