Design, synthesis, and biological evaluation of conformationally constrained cis-amide HSP90 inhibitors

Adam S. Duerfeldt; Gary E.L. Brandt; Brian S.J. Blagg

doi:10.1021/ol900783m

Design, synthesis, and biological evaluation of conformationally constrained cis-amide HSP90 inhibitors

Adam S. Duerfeldt, Gary E.L. Brandt, Brian S.J. Blagg

Research output: Contribution to journal › Article › peer-review

24 Scopus citations

Abstract

Conformationally constrained cis-amide chimeric inhibitors of Hsp90 have been synthesized and evaluated for their Hsp90 inhibitory activity. These new compounds exhibited Hsp90 ATPase inhibition and induced Hsp90-dependent client protein degradation in a dose-dependent manner. Biological data reported herein suggests that amide bond isomerization of geldanamycin derivatives plays an important role in affinity for the heteroprotein complex present in cancer cells.

Original language	English (US)
Pages (from-to)	2353-2356
Number of pages	4
Journal	Organic Letters
Volume	11
Issue number	11
DOIs	https://doi.org/10.1021/ol900783m
State	Published - Jun 4 2009
Externally published	Yes

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abstract = "Conformationally constrained cis-amide chimeric inhibitors of Hsp90 have been synthesized and evaluated for their Hsp90 inhibitory activity. These new compounds exhibited Hsp90 ATPase inhibition and induced Hsp90-dependent client protein degradation in a dose-dependent manner. Biological data reported herein suggests that amide bond isomerization of geldanamycin derivatives plays an important role in affinity for the heteroprotein complex present in cancer cells.",

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Design, synthesis, and biological evaluation of conformationally constrained cis-amide HSP90 inhibitors

Abstract

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