Synthetic approaches to indolo[6,7-a]pyrrolo[3,4-c]carbazoles:: Potent cyclin D1/CDK4 inhibitors

Synthesis of indolo[6,7-alpha]pyrrolo[3,4-c]carbazoles 1, a new class of cyclin D1/CDK4 inhibitors, by oxidation of the corresponding aryl indolylmaleimides 2, will be described. Two approaches to the synthesis of 2 were identified that required new methods for the synthesis of 7-substituted indole acetamides 3 and N-methyl (indol-7-yl)oxoacetates 6. The chemistry developed enabled introduction of functionality (-OR, NR2) at C-12 and N-13 facilitating structure-activity relationship (SAR) evaluation of this indolocarbazole platform.