Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
1373428 | Bioorganic & Medicinal Chemistry Letters | 2010 | 4 Pages |
We describe the development of a novel series of N-aryl-benzimidazolone HSP90 inhibitors (9) targeting the N-terminal ATP-ase site. SAR development was influenced by structure-based design based around X-ray structures of ligand bound HSP90 complexes. Lead compounds exhibited high binding affinities, ATP-ase inhibition and cellular client protein degradation.
Graphical abstractWe describe the development of a novel series of N-aryl-benzimidazolone HSP90 inhibitors targeting the N-terminal ATP-ase site. SAR development was influenced by structure-based design based around X-ray structures of ligand bound HSP90 complexes. Lead compounds exhibited high binding affinities, ATP-ase inhibition and cellular client protein degradation.Figure optionsDownload full-size imageDownload as PowerPoint slide