Table 1.
Residual ALK5 and p38α MAP kinase activities in the presence of 3-substituted-4-(quinoxalin-6-yl) pyrazoles 14a–d, 15a–d, 16a–d, 17a–d, 18a–d, and 19a–d.
| Compounds | R | X | Residual Activity a (%) | |
|---|---|---|---|---|
| p38α b | ALK5 c | |||
| 14a | H | O | 110 | 85 |
| 14b | o-F | O | 118 | 84 |
| 14c | m-F | O | 121 | 37 |
| 14d | m-CN | O | 121 | 95 |
| 15a | H | 118 | 95 | |
| 15b | o-F | 117 | 87 | |
| 15c | m-F | 109 | 88 | |
| 15d | m-CN | 109 | 94 | |
| 18a | H | S | 119 | 29 |
| 18b | o-F | S | 125 | 70 |
| 18c | m-F | S | 165 | 29 |
| 18d | m-CN | S | 119 | 54 |
| 16a | H | O | 98 | 5 |
| 16b | o-F | O | 103 | 5 |
| 16c | m-F | O | 101 | 3 |
| 16d | m-CN | O | 108 | 3 |
| 17a | H | 68 | 46 | |
| 17b | o-F | 54 | 73 | |
| 17c | m-F | 66 | 69 | |
| 17d | m-CN | 97 | 58 | |
| 19a | H | S | 102 | 5 |
| 19b | o-F | S | 92 | 2 |
| 19c | m-F | S | 109 | 2 |
| 19d | m-CN | S | 105 | 13 |
| 3 (LY-2157299) | 4 | 1 | ||
a Residual kinase activities were measured with each compound at 10 μM, in duplicate, in reactions containing p38α and ALK5 protein kinases. b p38α MAP kinase was expressed in E. coli as the untagged human recombinant protein. The enzyme was purified by Ni-NTH–agarose (Qiagen). A proprietary radioisotopic protein kinase assay (33PanQinase® Activity Assay) was performed at ProQinase GmbH (Freiburg, Germany), using ATF2 as a substrate. c ALK5 was expressed in Sf9 insect cells as the human recombinant GST-fusion protein using the vaculovirus expression system. A proprietary radioisotopic protein kinase assay (33PanQinase® Activity Assay) was performed at ProQinase GmbH (Freiburg, Germany) using casein as a substrate.