(AMINOALKYL)AMINO]BENZO[G]ISOQUINOLINE-5,10-DIONES - A NOVEL CLASS OFCHROMOPHORE-MODIFIED ANTITUMOR ANTHRACENE-9,10-DIONES - SYNTHESIS ANDANTITUMOR EVALUATIONS

Synthetic procedures have been developed which lead to the 2-aza conge ners 3 and several related N-oxides 4. The analogues 3 exhibited a wid e range of in vitro cytotoxicity against L1210 leukemia, the human col on adenocarcinoma cell line LoVo, and the doxorubicin resistant LoVo/D X cell line. Selected analogues of 3 showed significant P388 antileuke mic activity in mice with 3c exhibiting high activity. This activity w as also retained in the related N-oxide 4a. These heterocyclic bioisos teric models are representative of the first anthracene-9,10-diones wh ich display antileukemic activity comparable to mitoxantrone.