Intensely potent morpholinyl anthracyclines.
3'-Deamino-3'-(3-cyano-4-morpholinyl)doxorubicin is a new analogue that is 100 to 1000 times more potent than doxorubicin against tumors in cell culture or in mice, that is active by intraperitoneal, intravenous, or oral dosing, and that does not produce chronic myocardial lesions in mice. This analogue was encountered in studies on the reductive alkylation of doxorubicin and daunorubicin with 2,2' - oxybis [acetaldehyde], which constructs a morpholino ring incorporating the amino N. The morpholinyl nitrile byproducts are separated by virtue of their nonbasicity from the expected morpholino derivatives. The 13-dihydro and 5-imino derivatives are also described in this important new class of anthracyclines.
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity; D004353:Drug Evaluation, Preclinical; D007202:Indicators and Reagents; D007939:Leukemia L1210 / Q000188:drug therapy; D007941:Leukemia P388 / Q000188:drug therapy; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D051379:Mice; D013329:Structure-Activity Relationship
D000903:Antibiotics, Antineoplastic; D007202:Indicators and Reagents; D004317:Doxorubicin; C038555:3'-deamino-3'-(3-cyano-4-morpholinyl)doxorubicin