Enhanced Antitumor Properties of 3'-(4-Morpholinyl) and 3'-(4-Methoxy-1-piperidinyl) Dervatives of 3'-Deaminodaunorubicin

Article abstract of DOI:10.1021/jm00343a004

Reductive N,N-dialkylation of daunorubicin with 2,2'-oxydiacetaldehyde and NaBH3CN occurred in two steps without interruption and with cyclization to form 3'-(4-morpholinyl)-3'-deaminodaunorubicin.This derivative retained the antitumor efficacy of doxorubicin against mouse leukemia P388 but at one-fortieth the dose; hence, it is the most potent anthracycline analogue synthesized so far.The 4-methoxy-1-piperidinyl derivative, similarly prepared with 3-methoxyglutaraldehyde, showed improved efficacy against P388, though at normal doses.Results with a series of analogues indicate that incorporation of the N in the new ring and the presence of an ether O at the 4-position are critical for enhanced activity.