Enediyne quinone imines and methods of preparation and use thereof

摘要

PCT No. PCT/US95/15678 Sec. 371 Date Oct. 16, 1997 Sec. 102(e) Date Oct. 16, 1997 PCT Filed Dec. 1, 1995 PCT Pub. No. WO96/16655 PCT Pub. Date Jun. 6, 1996A quinone imine enediyne possessing cytotoxic activity towards cancer cells having general structure (I) wherein R1, R2 and R3 are independently the same or different and are H, Br, Cl, F, NH2, CO2H, OH, linear or branched alkyl, etc.; wherein R4 is H, OH or linear or branched alkoxy, linear or branched alkoxycarbonyl, etc.; wherein R5 is H, Br, Cl, F, O=, OH or S-SR, or linear or branched alkyl, etc.; wherein R6 is H, Br, Cl, F, CO2H, OH or S-SR', or linear or branched alkyl, etc.; wherein R7 is H, OH or S-SR'', or linear or branched alkyl, linear or branched alkoxycarbonyl, linear or branched alkoxy or linear or branched hydroxyalkyl; and wherein R, R' and R'' are independently the same or different and are linear or branched alkyl, linear or branched acyl or linear or branched alkoxyalkyl. Also provided are conjugates of the compound with cleavable peptides, enzymes, carbohydrates and monoclonal antibodies immunoreactive with cancer cells, as well as compositions comprising the analogues and conjugates, and methods of synthesis and treatment of tumors.