Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1370993 | Bioorganic & Medicinal Chemistry Letters | 2011 | 6 Pages |
Abstract
A novel series of macrocyclic ortho-aminobenzamide Hsp90 inhibitors is reported. In continuation of our research in this area, macrocyclic amides and lactams were explored to reduce the risk of hERG liabilities. This effort culminated in the discovery of compound 38, which showed a favorable in vitro profile, and efficiently suppressed proliferation of several relevant cell lines. This compound showed prolonged Hsp90-inhibitory activity at least 24 h post-administration, consistent with elevated and prolonged exposure in the tumor.
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Physical Sciences and Engineering
Chemistry
Organic Chemistry
Authors
Christoph W. Zapf, Jonathan D. Bloom, Jamie L. McBean, Russell G. Dushin, Thomas Nittoli, Mercy Otteng, Charles Ingalls, Jennifer M. Golas, Hao Liu, Judy Lucas, Frank Boschelli, Yongbo Hu, Erik Vogan, Jeremy I. Levin,