Table 2. Additional Miscellaneous SAR.
compda | R1 | R2 | X | Y | IC50 (μM)b |
---|---|---|---|---|---|
24 | NHCO2tBu | H | CH | CH | 0.262 ± 0.039 |
45 | H | H | CH | CNHCO2tBu | 11.06 ± 0.33 |
46 | NHCO2tBu | H | CH | N | 0.309 ± 0.010 |
47 | NHCO2tBu | H | N | CH | 0.372 ± 0.038 |
48 | NHCO2tBu | Mec | CH | CH | 0.0274 ± 0.0012 |
49 | NHCO2tBu | Phec | CH | CH | 0.172 ± 0.075 |
50 | NHCO2iPr | Mec | CH | N | 0.002 ± 0.001 |
51 | oxazolidinone | H | CH | CH | 5.16 ± 0.07 |
52 | CO2H | H | CH | CH | inactive |
53 | CO2Me | H | CH | CH | 1.64 ± 0.27 |
54 | CO2iPr | H | CH | CH | 0.110 ± 0.049 |
55 | OCOiPr | H | CH | CH | 5.45 ± 0.23 |
56 | CONMe2 | H | CH | CH | 5.91 ± 0.27 |
57 | CONHtBu | H | CH | CH | inactive |
All compounds are racemates.
IC50 values represent the half maximal (50%) inhibitory concentration for the Bcl-2–Beclin 1 BH3 interaction as determined in the AlphaLISA assay. Error represents SD (n = 3). All compounds were inactive (at 10 μM) against the Bcl-2–Bax BH3 interaction except compounds 50 (IC50 = 0.157 ± 0.048 μM) and 54 (IC50 = 4.36 ± 0.03 μM).
Single diastereomer; configuration not assigned.