Synthesis and antitumor evaluation of selected 5,6-disubstituted 1(2)H-indazole-4,7-diones.
A series of novel aziridinyl-substituted 1(2)H-indazole-4,7-diones and related 1(2)H-indazole-4,7-diones was synthesized and tested against Ehrlich ascites carcinoma growth in male CF1 mice. Ten of the test compounds, including two aziridinyl-substituted 1(2)H-indazole-4,7-diones, were found to be significantly active (inhibition of tumor growth greater than 80%) in the Ehrlich ascites carcinoma screen. Several structure-activity relationships were indicated for antitumor activity in this screen. An aziridinyl-substituted derivative, 5-aziridinyl-6-chloro-1H-indazole-4,7-dione (8a), also exhibited significant activity against the growth of P-388 lymphocytic leukemia cells in male BDF1 mice (% T/C = 145; % T/C greater than 125 is considered significant).
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis; D002286:Carcinoma, Ehrlich Tumor / Q000188:drug therapy; D002455:Cell Division / Q000187:drug effects; D007191:Indazoles / Q000138:chemical synthesis / Q000627:therapeutic use*; D007941:Leukemia P388 / Q000188:drug therapy; D008297:Male; D051379:Mice; D011720:Pyrazoles / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D007191:Indazoles; D011720:Pyrazoles