Macrocyclic lactams as potent Hsp90 inhibitors with excellent tumor exposure and extended biomarker activity.
Basic Information
ID: ALA1777797
Journal: Bioorg Med Chem Lett
Title: Macrocyclic lactams as potent Hsp90 inhibitors with excellent tumor exposure and extended biomarker activity.
Authors: Zapf CW, Bloom JD, McBean JL, Dushin RG, Nittoli T, Otteng M, Ingalls C, Golas JM, Liu H, Lucas J, Boschelli F, Hu Y, Vogan E, Levin JI.
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.
CiteXplore: 21515049
DOI: 10.1016/j.bmcl.2011.03.112
Patent ID: ┄