Synthesis and SAR study of 4-hydroxy-3-(2-hydroxynapthalene-1-yl)phenyl)-arylsulfonamides: Heat shock protein 90 (Hsp90) inhibitors with submicromolar activity in an in vitro assay

• Type of Material: Article
• Authors: Thota Ganesh, Emory University; Pahk Thepchatri, Emory University; Lian Li, Emory University; Yuhong Du, Emory University; Haian Fu, Emory University; James P Snyder, Emory University; Aiming Sun, Emory University
• Language: English
• Date: 2008-09-15
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: ©2008 Elsevier Ltd. All rights reserved
• License: Creative Commons Attribution-NonCommerical-NoDerivs 3.0 Unported
• Final Published Version (URL): http://dx.doi.org/10.1016/j.bmcl.2008.08.022
• Title of Journal or Parent Work: Bioorganic and Medicinal Chemistry Letters
• ISSN: 0960-894X
• Volume: 18
• Issue: 18
• Start Page: 4982
• End Page: 4987
• Grant/Funding Information: This work was supported by the US National Institutes of Health 1 U54 HG003918-02 and 1R03MH076499-01 and encouraged by Professor Dennis Liotta (Emory University)
• Keywords: Structure-based design; Heat shock protein 90; Suzuki-coupling; Antiproliferative activity; FP assay; Sulfonamides
• Research Categories: Health Sciences, Pharmacology; Chemistry, General; Health Sciences, Pathology

Abstract

Heat shock protein 90 is emerging as an important target in cancer chemotherapy. In a program directed towards identifying novel chemical probes for Hsp90, we found 4-hydroxy-3-(2-hydroxynapthalene-1-yl)phenyl)benzene sulfonamide as an Hsp90 inhibitor with very weak activity. In this report we present a new and general method for the synthesis of variety of analogs around this scaffold and discuss their structure activity relationships.