Table 1.
SAR around the side chain S-R2, sulfonamide moiety R1 of compound 1.
| Compound ID | S-R2 | R1 | IC50a (μM) Proteasome Activity (In Vitro) | |
|---|---|---|---|---|
| CT-L | T-L | |||
| 1 (15a and 11a) | S-CH2COOH |
|
3.0 ± 1.6 | ND |
| 15b |
|
|
4.2 ± 2.1 | ND |
| 15c |
|
|
4.2 ± 2.7 | ND |
| 24 |
|
|
4.05 ± 2.64 | ND |
| 25 |
|
|
0.28± 0.8 | 4.22 ± 0.30 |
| 26 |
|
|
0.73 ± 0.03 | 2.35 ± 0.05 |
| 27 |
|
|
0.18 ± 0.08 | 2.37 ± 0.05 |
| 28 |
|
|
0.3 ± 0.07 | 7 ± 0.8 |
| 29 |
|
|
0.150 ± 0.05 | 4.2 ± 1.8 |
| 30 |
|
|
2.47 ± 0.52 | 7.2 ± 0.9 |
| 31 |
|
|
1.97 ± 0.08 | ND |
| 32 |
|
|
1.61 ± 0.06 | ND |
| 33 |
|
|
0.30± 0.01 | 2.0 ± 0.2 |
| 34 |
|
|
0.65 ± 0.09 | ND |
| 15d |
|
|
0.51 ± 0.12 | 0.20 ± 0.10 |
| 15e |
|
|
0.22 ± 0.06 | 4.80 ± 0.54 |
| 15f |
|
|
0.23 ± 0.02 | 0.55 ± 0.32 |
| 15g |
|
|
0.480 ± 0.09 | 1.55 ± 0.45 |
| 15h |
|
|
0.23 ± 0.08 | 1.85 ± 0.67 |
| 15i |
|
|
0.40 ± 0.12 | 2.80 ± 0.12 |
| 15j |
|
|
0.23 ± 0.1 | 2.0 ± 0.60 |
| 15k |
|
|
0.22 ± 0.01 | 1.3 ± 0.4 |
| 15l |
|
|
0.40 ± 0.14 | 1.35 ± 0.56 |
| 15m |
|
|
0.47 ± 0.18 | 1.45 ± 0.14 |
| 35 |
|
|
0.570 ± 0.06 | 0.75 ± 0.13 |
| 36 |
|
|
0.54 ± 0.08 | 0.57 ± 0.31 |
| 37 |
|
|
0.6 ± 0.1 | 1.38 ± 0.60 |
| 38 |
|
|
0.63 ± 0.1 | 1.10 ± 0.16 |
| 39 |
|
|
0.88 ± 0.56 | 1.14 ± 0.16 |
a
Each IC50 is at least the mean of 3 determinations.
ND-IC50 not determined, these compounds showed less than 70% T-L inhibition at 10 μM.