Literature

Abstract

Previously, we identified 1-(2-(4-bromophenoxy)ethoxy)-3-(4-(2-methoxyphenyl)piperazin-1-yl)propan-2-ol (1) as a novel Hsp90 inhibitor with moderate activity through virtual screening. In this study, we report the optimization process of 1. A series of analogues containing the 1-phenylpiperazine core scaffold were synthesized and evaluated. The structure-activity relationships (SAR) for these compounds was also discussed for further molecular design. This effort afforded the most active inhibitor 13f with improved activity in not only target-based level, but also cell-based level compared with the original hit 1.

DOI： 10.1016/j.bmcl.2014.01.070

Synthesis and evaluation of a novel class Hsp90 inhibitors containing 1-phenylpiperazine scaffold

Bioorganic & Medicinal Chemistry Letters 2014.0

Synthesis and Biological Activities of a New Class of Heat Shock Protein 90 Inhibitors, Designed by Energy-Based Pharmacophore Virtual Screening

Journal of Medicinal Chemistry 2013.0

The identification, synthesis, protein crystal structure and in vitro biochemical evaluation of a new 3,4-diarylpyrazole class of Hsp90 inhibitors

Bioorganic & Medicinal Chemistry Letters 2005.0

4-Amino derivatives of the Hsp90 inhibitor CCT018159

Bioorganic & Medicinal Chemistry Letters 2006.0

Tricyclic Series of Heat Shock Protein 90 (Hsp90) Inhibitors Part I: Discovery of Tricyclic Imidazo[4,5-c]pyridines as Potent Inhibitors of the Hsp90 Molecular Chaperone

Journal of Medicinal Chemistry 2011.0

Synthesis and in vitro antiproliferative activity of C5-benzyl substituted 2-amino-pyrrolo[2,3- d ]pyrimidines as potent Hsp90 inhibitors