The residue was purified by column chromatography (SiO2; 3:1, Hex:EtOAc) to afford acetamide 17 (0.17 g, 74%). and 5 g/ml blasticidin. The cells were transfected using lipofectamine and after 24 h, were re-seeded into 24 well plates at a density of 2 105 cells per well. The cells were permitted to attach to the plate for 6 h in growth medium and treated with the indicated concentrations of the various novologues for 16 h. Luciferase activity was assessed and normalized to the total protein concentration of each well. Results shown are from triplicate wells obtained in at least three individual experiments. Preliminary experiments validated that this reporter was strongly activated as expected by either heat shock (~ 10 fold) or 250 nM geldanamycin (~4C5 fold). Client protein degradation in MCF7 cells was performed as we have previously described. Molecular Modeling Surflex-Dock in Sybyl v8.0 was used for molecular modeling and docking studies. A homology model of Hsp90 based on the open HtpG SAXS structure was used as the receptor, while the protomol was generated using docked Novobiocin as described in reference.13 The energy minimized molecules were then docked with 10 different starting conformations while rotation of rotatable bonds was unrestricted. Visual interpretation and physique preparation were then carried out in Pymol. Chemistry General 1H NMR were recorded at 400 or 500 MHz (Bruker DRX-400 Bruker with a H/C/P/F QNP gradient probe) spectrometer and MT-3014 13C NMR spectra were recorded at 125 MHz (Bruker DRX 500 with broadband, inverse triple resonance, and high resolution magic angle spinning HR-MA probe spectrometer); chemical shifts are reported in (ppm) relative to the internal reference chloroform-d (CDCl3, 7.27 ppm). FAB (HRMS) spectra were recorded with a LCT Premier (Waters Corp., Milford, MA). The purity of all compounds was decided to be 95%as determined by 1H NMR and 13C NMR spectra, unless otherwise noted. The most active 5 compounds were verified for 95% purity by HPLC analyses. TLC was performed on glass MT-3014 backed silica gel plates (Uniplate) with spots visualized by UV light. All solvents were reagent grade and, when necessary, were purified and dried by standard methods. Concentration of solutions after MT-3014 reactions and extractions involved the use of a rotary evaporator operating at reduced pressure. 5-(Benzyloxy)-2-formylphenyl trifluoromethanesulfonate (7) Triethylamine (1.02 mL, 7.35 mmol) followed by triflic anhydride (1.38 mL, 6.35 mmol) were added simultaneously to a phenol 6 (1.12 g, 4.91 mmol) in anhydrous CH2Cl2 (10 mL) at 0 C. Upon completion of the reaction, quenched by the addition of water CD40 (50 mL), extracted with CH2Cl2 (3 15 mL), washed with saturated aqueous sodium chloride solution, dried over anhydrous Na2SO4, filtered and concentrated. The residue was purified by column chromatography (SiO2, 4:1, Hex:EtOAc) to afford triflate 7 as a yellow oil (1.06 g, 60%). General procedure for Suzuki coupling reaction of triflate 3 and boronic acids 4aCp: 5-(Benzyloxy)-[1,1′-biphenyl]-2-carbaldehyde (8a) Tetrakis(triphenylphosphine)palladium(0) (70.4 mg, 0.068 mmol) was added to a mixture of MT-3014 triflate 7 (0.246 g, 0.68 mmol), phenylboronic acid 4a (92 mg, 0.75 mmol), and K2CO3 (0.169 g, 1.2 MT-3014 mmol) in DMF (6.8 mL) under argon atmosphere in a sealed tube. The resulting reaction mixture was sealed and heated to reflux for 16 h. The reaction was cooled to room temperature, quenched with saturated sodium bicarbonate, extracted with EtOAc (3 5 mL), washed with saturated aqueous sodium chloride, dried over anhydrous Na2SO4, filtered and concentrated. The crude product was purified by column chromatography (SiO2, 3:1, Hex:EtOAc) to afford 8a (0.16 g, 0.56 mmol, 82%) as an amorphous solid. 1H NMR (400 MHz, CDCl3) 9.90 (s, 1H), 8.08 (d, = 8.7 Hz, 1H), 7.55 C 7.34 (m, 10H), 7.11 (d, = 8.7 Hz, 1H), 7.0 3 (d, = 2.4 Hz, 1H), 5.19 (s, 2H); 13C NMR (100.