Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10587718 | Bioorganic & Medicinal Chemistry Letters | 2013 | 5 Pages |
Abstract
Cdc7 kinase is responsible for the initiation and regulation of DNA replication and has been proposed as a target for cancer therapy. We have identified a class of Cdc7 inhibitors based on a substituted indole core. Synthesis of focused indole and azaindole analogs yielded potent and selective 5-azaindole Cdc7 inhibitors with improved intrinsic metabolic stability (ie 36). In parallel, quantum mechanical conformational analysis helped to rationalize SAR observations, led to a proposal of the preferred binding conformation in the absence of co-crystallography data, and allowed the design of 7-azaindole 37 as a second lead in this series.
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Authors
Marian C. Bryan, James R. Falsey, Mike Frohn, Andreas Reichelt, Guomin Yao, Michael D. Bartberger, Julie M. Bailis, Leeanne Zalameda, Tisha San Miguel, Elizabeth M. Doherty, John G. Allen,