Table 2.
Inhibition of GSK-3β by Maleimides 21–31.
| |||||
|---|---|---|---|---|---|
| Cmpd. | R1 | R2 | R3 | R4 | IC50 (nM)a |
| 21 | H | Me | Me | - | 11.2±3.1 |
| 22 | H | Me | t-Bu | - | 148±15 |
| 23 | H | -(CH2)2OMe | Me | - | 114±16 |
| 24 | H | - | - | - | 4.2±0.7 |
| 25 | F | - | - | - | 3.7±0.5 |
| 26 | Br | - | - | - | 11.5±2.2 |
| 27 | H | - | - | 2-pyrazinyl | 0.20±0.06 |
| 28 | H | - | - | 4-pyridylmethyl | 0.59±0.11 |
| 29 | F | - | - | 1-piperidinyl | 1.9±0.4 |
| 30 | F | - | - | 4-piperidinopiperidin1-yl | 0.53±0.01 |
| 31 | F | - | - | 4-morpholinyl | 0.013±0.005 |
The synthesized maleimides were evaluated for their ability to inhibit phosphorylation of primed substrate (YRRAAVPPSPSLSRHSSPHQ(pS)EDEEE; 20 μM) by human GSK-3β in the presence of 10 μM ATP concentration. These compounds were tested at Reaction Biology Inc.37 and IC50 values are presented as either average of duplicates ± SEM.