Table 2. SAR in Pyridine Seriesa.
compound | T. b. brucei EC50 [nM] | T. b. brucei proteasome IC50/human proteasome [nM] | LM CLint M/R/H [μL/min/mg] | MDCK-MDR1 A to B (ER) [10–6 cm/s] |
---|---|---|---|---|
13 | 46 | 17/>10 000 | 394/114/62 | 13.5 (0.6) |
14 | 13 | 19/>10 000 | 91/48/<25 | 12.8 (0.6) |
15 | 60 | 95/43/<25 | 13.8 (0.7) |
Details on the biochemical and cellular assay as well as on clearance (Clint) and permeability (MDCK-MDR1) can be found in the Experimental Section.