Table 4.
Summary of acrylamides 7a–g: Yield, IC50 values of the inhibition between coregulatory peptide SRC2-2 and TRα/TRβ, viability (LD50) of U2OS and ARO cells in the presence of compound, solubility in PBS buffer containing 5% DMSO, and permeability across an artificial membrane (PAMPA).
| In vitro Potency | Cytotoxicity | Pharmacological Properties | ||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Entry | R = 4-hexylbenzene | Compound | Yielda (%) | TRαb IC50 (μM) | TRβb IC50 (μM) | TRα: TRβ ratio | AROc LD50 (μM) | U2OSc LD50 (μM) | Solubility (μM) | Permeability (10−6 cm/s) |
| 1 |
|
7a | 88 | 21.6 | 20.3 | 1.1 | 113 | 66.5 | 47 | 833 |
| 2 |
|
7b | 85 | 17.5 | 17.9 | 1.0 | >200 | 148 | 418 | 29 |
| 3 |
|
7c | 78 | >100 | >100 | - | >200 | >200 | 42 | 432 |
| 4 |
|
7d | 84 | >100 | >100 | - | >200 | >200 | 37 | 98 |
| 5 |
|
7e | 89 | >100 | >100 | - | 174 | 69.4 | 105 | 14 |
| 6 |
|
7f | 80 | >100 | >100 | - | 183 | 124 | 286 | 57 |
| 7 |
|
7g | 78 | >100 | >100 | - | .>200 | >200 | 372 | 48 |
a
Isolated yield;
b
values are means of two independent experiments done in quadruplicate; the general error limits are 10%;
c
values are means of two independent experiments done in triplicate; the general error limits are 10–15%. Actual error values for each measurement are omitted for clarity but are included in tables in the supplemental materials.