Table 2.
Inhibition of HIV-1 integrase catalytic activities, integrase-LEDGF/p75 interaction, and cytotoxicity of the 2,3-dihydroxybenzamide series with variations on the phenyl ring and the carboxamide moiety.
 | ||||||
|---|---|---|---|---|---|---|
| Compd. | R1 | R2 | IC50 (μM) | IC50 (μM) LEDGF/p75-IN | CC50 (μM) H630 cells | |
| 3′-Processing | Strand transfer | |||||
| 5a | H |
|
>100 | 35 ± 25 | > 100 | > 40 |
| 5c | H |
|
>100 | 26± 4 | 34± 9 | 21 |
| 5d | H |
|
>100 | 23 ± 7 | 56±8 | > 40 |
| 5e | H |
|
>100 | 24 ± 2 | 45± 9 | > 40 |
| 5f | H |
|
100 | 100 | 63± 20 | 15 |
| 5g | H |
|
>100 | 58± 12 | 88± 19 | > 40 |
| 5h | H |
|
83±21 | 12±4 | 95± 11 | > 40 |
| 5i | H |
|
90±14 | 15±5 | 89±8 | > 40 |
| 5j | H |
|
> 100 | 21± 5 | > 100 | 15 |
| 5k | H |
|
> 100 | > 100 | > 100 | > 10 |
| 5l | H |
|
> 100 | > 100 | > 100 | > 40 |
| 5m | H |
|
> 100 | 18±9 | > 100 | 21 |
| 5n | H |
|
>100 | 56 ± 19 | > 100 | > 40 |
| 5o | H |
|
> 100 | 100 | > 100 | > 40 |
| 5p |
|
|
200 | 5 | ND | 13 |
| 5q | -SO2NHMe |
|
>100 | 44 ± 7 | > 100 | > 40 |
| 5r | -SO2NHtBu |
|
70 | 8±5 | 100 | > 10 |
| 5s |
|
|
> 100 | 13 | > 100 | 33 |
| 5t |
|
|
89 | 11 | > 100 | 31 |
| 5u |
|
|
53±4 | 19±3 | 8± 1 | >40 |
| 5v |
|
|
> 100 | 44±19 | > 50 | >40 |
| 5w |
|
|
> 100 | 34±10 | 100 | |
| 5x |
|
|
55±7 | 14±4 | > 100 | < 10 |
| 5y | CN |
|
75±7 | 22±8 | ND | > 10 |
| 6a |
|
> 100 | 20±4 | > 50 | > 10 | |
| 6b |
|
> 100 | 39±8 | > 50 | 7 | |
| 6c |
|
>100 | > 100 | 13±4 | > 25 | |
| 6d |
|
> 100 | > 100 | 51±4 | > 25 | |