Table 5.
Biological activity and selected ADME data for headgroup truncation and replacement analogs.
| ID | Core | R | T.b.b. pEC50 | MRC5 pTC50 | LLE | Aq. sol. (μM) | cLogP |
|---|---|---|---|---|---|---|---|
| 28a |  |
 |
4.8 | <4.3 | 4.1 | 65 | 0.61 |
| 28b |  |
5.4 | <4.3 | 4.7 | nd | 0.76 | |
| 31a |  |
 |
4.8 | <4.3 | 4.2 | 58 | 0.64 |
| 31b |  |
4.8 | <4.3 | 4.0 | 5 | 0.79 | |
| 31c |  |
5.5 | <4.3 | 4.6 | <13 | 0.87 | |
| 34a |  |
 |
5.3 | <4.3 | 3.9 | 660 | 1.4 |
| 34b |  |
4.3 | <4.3 | 2.8 | 332 | 1.5 | |
| 34c |  |
5.2 | <4.3 | 3.6 | 215 | 1.6 | |
| 40 |  |
 |
5.9 | <4.3 | 3.4 | 0.3 | 2.6 |
| 49 |  |
 |
7.1 | <4.3 | 5.3 | 13 | 1.8 |
| 50* |  |
 |
8.2 | 5.9 | 5.1 | 10 | 1.4 |
| 51* |  |
 |
6.2 | 4.0 | 5.2 | >100 | 0.71 |
†
Kinetic aqueous solubility.
*
Compound and data provided by GSK; HepG2 toxicity and kinetic aqueous solubility.
All SD within ± 0.19.