Hadden, M. Kyle S. J. Blagg, Brian Synthesis and Evaluation of Radamide Analogues, A Chimera of Radicicol and Geldanamycin Previously, we reported the Hsp90 inhibitory activity of radamide, an open chain amide chimera of geldanamycin and radicicol. Attempts to further expand upon structure−activity relationships for this class of Hsp90 inhibitors led to the preparation of a series of radamide analogues focused on differing tether lengths and quinone mimics. In addition, the cup-shaped conformation adopted by the two natural products when bound to the Hsp90 N-terminal ATP binding pocket suggests that conformationally biased compounds may demonstrate improved binding and inhibition. The preparation and evaluation of radamide analogues with <i>cis</i>/<i>trans</i> α,β-unsaturated amides yielded compounds that exhibit improved antiproliferative activity. In addition, several analogues demonstrated the ability to induce degradation of Hsp90-dependent oncogenic signaling proteins in vitro, a hallmark of Hsp90 N-terminal inhibition. Hsp 90 inhibitors;binding;ATP;preparation;chain amide chimera;radamide analogues;inhibition;compound 2009-07-03
    https://acs.figshare.com/articles/journal_contribution/Synthesis_and_Evaluation_of_Radamide_Analogues_A_Chimera_of_Radicicol_and_Geldanamycin/2845894
10.1021/jo900278g.s001