Figure 1.

Structures of QT₂C₂ (1) and QT₂C₂Me₂ (8) and stability analysis. (A) The hindered dimer prodrug, QT₂C₂Me₂ (8), was synthesized as in Scheme 1 using a dicarboxylic acid linker (2,3-dimethylsuccinic acid). The prodrugs were purified to homogeneity by reverse phase HPLC, purity confirmed by analytical HPLC, and structures confirmed by MALDI-TOF mass spectrometry. (B) QT₂C₂ (1) and QT₂C₂Me₂ (8) (40 μM each) were incubated in the presence of human plasma (55% in 10 mM phosphate buffer, pH 7.4) or 10 units of pig liver esterase at 37 °C. Reversion of the prodrugs to monomer was quantified via analytical HPLC and normalized to an internal standard. t_1/2 values for stability in human plasma represent duplicate experiments ± SD.