Table 1.
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IC50a Values (nM) |
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Cmpd | R1 | R2 | R3 | R4 | X | Cat L | Cat B |
1 | H | H | H | H | C=O | 9.9 | >10000 |
2 | H | H | H | Bz | C=O | 56.0 | >10000 |
4 | H | H | H | H | CH(OH) | 23.8 | >10000 |
8 | F | H | H | H | C=O | 14.4 | >10000 |
9 | Br | H | H | H | C=O | 1522 | >10000 |
10 | Br | H | H | H | C=NNHC(S)NH2 | >10000 | >10000 |
11 | OCH3 | H | H | H | C=O | 5117 | >10000 |
13 | OH | H | H | H | C=O | 340 | >10000 |
14 | OCH(CH3)2 | H | H | H | C=O | >10000 | >10000 |
20 | H | CH3 | H | H | C=O | 654 | >10000 |
22 | H | Br | H | OH | C=O | ~10000b | >10000 |
31 | H | OH | H | Br | C=O | 71.6 | >10000 |
32 | H | H | F | Br | C=O | 8.1 | >10000 |
33 | H | Br | H | Br | C=O | 10347 | >10000 |
These values are averages of a minimum of a triplicate of experiments. Each assay utilized 2% DMSO with a 5 min pre-incubation period. Standard error values can be found in the Supplementary data.
Compound 22 inhibited cathepsin L activity by 56.9% at 10000 nM.