Table 3. Combining R2 and R3 SAR.
| ||||||
| R2 | R3 | TYK2 JH2 (IC50, μM) | IL23/IFNα (IC50, μM) | PDE4 (IC50, μM) | LM a % rem (h/r/m) | |
| 18 |
|
|
0.007 | 0.10/0.05 | 0.062 | 15/21/6 |
| 23 |
|
|
0.008 | 0.11/0.10 | 0.006 | 11/14/1 |
| 24 |
|
|
0.002 | 0.30/0.11 | 0.015 | 20/4/0 |
| 25 |
|
|
0.015 | 0.48/0.33 | 0.018 | 70/16/0 |
| 26 |
|
|
0.006 | 0.02/0.01 | 0.024 | 52/9/0 |
| 27 |
|
|
0.005 | 0.15/0.12 | 0.088 | 85/40/2 |
| 28 |
|
|
0.006 | 0.07/0.03 | 0.032 | 100/34/24 |
| 29 |
|
|
0.004 | 0.24/0.16 | 0.043 | 99/76/44 |
| 30 |
|
|
0.008 | 0.30/0.45 | 0.013 | 100/40/26 |
aLM % rem (h/r/m) refers to liver microsomal stability in human/rat/mouse as measured by % remaining.20