Table 4. Overall Profiles for Compounds 4, 14, 23, 31, and 32.
| 4 | 14 | 23 | 31 | 32 | |
|---|---|---|---|---|---|
| MW, clogD, PSA | 416, 2.7, 85 | 416, 3.0, 95 | 395, 2.7, 91 | 400, 3.0, 85 | 431, 3.2, 95 |
| THP-1 (MCP-1) IC50 (μM) | 0.13 | 0.18 | 0.60 | 0.38 | 0.20 |
| MDCK-MDRI E.R./PappA-B | 10/8 | 2/10 | 12/4 | 2/16 | 0.9/34 |
| Rat B/Pa | 0.013 | 0.1 | 0.3 | ||
| CNS MPO | 5.0 | 4.6 | 5.1 | 4.9 | 4.3 |
| CYP 2C9 IC50 (μM) | 0.49 | 7 | 11 | 11 | 15 |
| Microsome stabilityb H/R | 92/100 | 89/69 | 100/73 | 56/51 | 79/100 |
| Protein binding % H/R | 98.11/98.88 | 94.12/92.96 | 98.66/>99 | >99/>99 | |
| DNA-PK Ki (μM) | 3.4 | 2.8 | >7 | >7 | 3.5 |
| hERG (Planar patch) IC50 (μM) | 13 | >30 | >30 | 28 | >30 |
| Kinase selectivity | >4 μM for 13 kinases | >4 μM for 13 kinases | >4 μM for 13 kinases | >4 μM for 13 kinases | >4 μM for 13 kinases |
a
Determined from 1 mg/kg oral dose, 1 h time point.
b
% Remaining after 30 min.