Journal of Organic Chemistry 2004-04-30

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

Margaret M Faul, Thomas A Engler, Kevin A Sullivan, John L Grutsch, Marcella T Clayton, Michael J Martinelli, Joseph M Pawlak, Michael LeTourneau, D Scott Coffey, Steven W Pedersen, Stanley P Kolis, Kelly Furness, Sushant Malhotra, Rima S Al-awar, James E Ray

Index: J. Org. Chem. 69 , 2967-2975, (2004)

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Abstract

Synthesis of indolo[6,7-a]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, NR(2)) at C(12) and N(13) facilitating structure-activity relationship (SAR) evaluation of this indolocarbazole platform.