CH5164840 (16) shows high binding affinity for N-terminal Hsp90a (K d = 0.52 nM) and strong anti-proliferative activity against human cancer cell lines (HCT116 IC 50 = 0.15 μM, NCI-N87 IC 50 = 0.066 μM). CH5164840 (16) is orally active (t 1/2 = 2.64 h) with potent antitumor efficacy.