Toluidinesulfonamide hypoxia-induced factor 1 inhibitors: alleviating drug-drug interactions through use of PubChem data and comparative molecular field analysis guided synthesis

Inhibitors of hypoxia-inducible factor 1 (HIF-1) represent promising anticancer therapeutics. We have identified a series of potent toluidinesulfonamide HIF-1 inhibitors. However, the series was threatened by a potential liability to inhibit CYP2C9 which could cause dangerous drug-drug interactions when being coadministered with other drugs. We used structure-activity data from the PubChem database to develop a topomer CoMFA model that guided the design of novel sulfonamides with high selectivity for HIF-1 over CYP2C9 inhibition.

Bernd Wendt, Marcel Mülbaier, Sabine Wawro, Christoph Schultes, Jorge Alonso, Bernd Janssen, Joe Lewis
June 9, 2011
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