Synthesis and use of dual tyrosyl-DNA phosphodiesterase I (TDP1)- topoisomerase I (TOP1) inhibitors

摘要

The invention described herein pertains to the synthesis and use of certain N-substituted indenoisoquinoline compounds which inhibit the activity Tyrosyl-DNA Phosphodiesterase I (Tdp1) or Topoisomerase I (Top1) or both, or otherwise demonstrate anticancer activity. Also disclosed are novel N-substituted indenoisoquinoline compounds and pharmaceutical compositions comprising the novel N-substituted indenoisoquinoline compounds.

主权项

1. A method for treating cancer comprising the step of administering a therapeutically effective amount of a compound of formulaor a pharmaceutically acceptable salt thereof,wherein:
RT is amino, Ra is 3-carboxymethylamino and Rd is hydrogen; or RT is amino, Ra is 3-amino and Rd is 9-methoxy; or RT is amino, Ra is 3-nitro and Rd is 8-methoxy; or RT is amino, Ra is 3-nitro and Rd is 7-methoxy; or RT is amino, Ra is 3-iodo and Rd is hydrogen; or RT is dimethylamino, Ra is 3-iodo and Rd is 9-methoxy; or RT is dimethylamino, Ra is 3-cyano and RQ is hydrogen; or RT is amino, Ra is 3-amino and Rd is hydrogen; or RT is amino, Ra is 3-nitro and Rd is 9-methoxy; or RT is amino, Ra is 3-iodo and Rd is 9-methoxy;to a patient in need of relief from said cancer.