SYNTHESIS AND EVALUATION OF TOPOISOMERASEI INHIBITORS POSSESSING THE 5,13-DIHYDRO-6H-BENZO6,7TNDOLO3,2-c-QUINOLIN-6-ONE SCAFFOLD

摘要

Novel topoisomerase I inhibitors possessing the 5,13-dihydro-6H-benzo6,7indolo3,2-cquinolin-6-one (BIQ) scaffold were designed and synthesized. This scaffold was constructed using sequential and regioselective mnctionalization of the pyrrole core through palladium-catalyzed cross-coupling, conventional electrophilic substitution, directed lithiation, and subsequent diphenylphosphoryl azide (DPPA)-mediated lactam ring construction. The obtained BIQs were evaluated for their topoisomerase I inhibitory activities and their antiproliferative activities in the panel of 39 human cancer cell lines established by the Japanese Foundation for Cancer Research (JFCR39).