Document Detail

Synthesis of a versatile metacyclophane macrolactam.
MedLine Citation:
PMID:  19568319     Owner:  NLM     Status:  Publisher    
As Hsp90 has emerged as a promising target for the development of cancer chemotherapeutics, so has the need for systematic evaluation of structure-activity relationships between natural product inhibitors and this molecular chaperone. Utilizing our chimera approach, which encompasses the quinone moiety of geldanamycin and the resorcinol moiety of radicicol, molecules have been produced that are highly effective inhibitors of the Hsp90 protein folding machinery. These chimeric inhibitors contain metacyclophane macrolactams that are difficult to cyclize and modify for incorporation of functional diversity. To circumvent this problem, a highly diversifiable alpha-bromo-alpha,beta-unsaturated ester has been prepared, which allows for the introduction of various functionalities that enable elucidation of structure-activity relationships between chimeric compounds and Hsp90. The rationale, synthesis, and optimization for such a molecule is reported herein.
Mingwen Wang; Brian S J Blagg
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Publication Detail:
Journal Detail:
Title:  Tetrahedron letters     Volume:  49     ISSN:  0040-4039     ISO Abbreviation:  Tetrahedron Lett.     Publication Date:  2008 Jan 
Date Detail:
Created Date:  2009-7-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  2984819R     Medline TA:  Tetrahedron Lett     Country:  -    
Other Details:
Languages:  ENG     Pagination:  141-144     Citation Subset:  -    
Department of Medicinal Chemistry, The University of Kansas, 1251 Wescoe Hall Drive, Malott 4070, Lawrence, KS 66045-7563.
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MeSH Terms
Grant Support
U01 CA109265-02//NCI NIH HHS

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