Novobiocin analogues with second-generation noviose surrogates

HSP90 is a promising therapeutic target for the treatment of Cancer. Novobiocin is the first HSP90 C-terminal inhibitor ever identified and recent structure-activity relationship studies on the noviose sugar identified several commercially available amines as suitable surrogates. In an effort to further understand this region of the molecule, analogues containing various N'-amino substituents were prepared and evaluated against two breast Cancer cell lines for determination of their efficacy. Compound 37j manifested the most potent anti-proliferative activity from these studies and induced Hsp90-dependent client protein degradation at mid nano-molar concentrations.