Table 3. Chemical Structure, Predicted ΔG* Values, PCSK9 Binding Affinity, and HMG-CoAR Inhibitory Activity Obtained for the Compounds Selected for the Synthesis.
| compound | R1 | R2 | ΔG* ± SEa (kcal/mol) | PCSK9/LDLR binding IC50 (μM) | HMG-CoAR activity IC50 (μM) |
|---|---|---|---|---|---|
| Dim2 | -(CH2)3t-Bu | -H | –35.9 ± 0.4 | 1.99 ± 1.65 | 40.48 ± 15.24 |
| Dim3 | - (CH2)3t-Bu | -C≡C—H | –38.0 ± 0.4 | 0.009 ± 0.01 | not active |
| Dim16 | -(CH2)3t-Bu | -I | –39.6 ± 0.2 | 0.0008 ± 0.001 | 146.8 ± 75.09 |
| Dim21 | -CH2Cy | -H | –29.8 ± 0.4 | 4.50 ± 0.50 | 38.4 ± 12.71 |
| Dim22 | -CH2Cy | -I | –32.6 ± 0.5 | 1.99 ± 2.86 | 36.21 ± 5.98 |
| Dim23 | -CH2Cy | -C≡C—H | –33.8 ± 0.5 | 1.18 ± 1.06 | not active |
a
Standard error of the mean value.