Table 1.
Inhibition of human NOS enzymes by 1,6-disubstituted indole derivatives
| |||||||
|---|---|---|---|---|---|---|---|
| Compound | X | R | nNOS IC50 a (μM) | eNOS IC50 a (μM) | iNOS IC50 a (μM) | eNOS/nNOS | iNOS/nNOS |
| 6 | S |
|
1.2 (0.99–1.3) | 15 (8.4–28) | 60 (37–98) | 13 | 50 |
| 7 | S |
|
0.49 (0.39–0.6) | 3.8 (1.1–12.2) | 21 (6.1–72) | 8 | 43 |
| (±)-8 | S |
|
0.22 (0.08–0.5) | 19 (11–33.9) | 68 (17–268) | 86 | 309 |
| (R)-8 | S |
|
0.32 (0.12–0.7) | 16 (6.6–38.2) | 72 (20–255) | 50 | 225 |
| (S)-8 | S |
|
0.2 (0.12–0.3) | 24 (15–37.1) | 72 (19.7–267) | 120 | 360 |
| 11 | S |
|
0.87 (0.46–1.65) | 37.7 (24.9–57.1) | NTb | 43 | NCc |
| 12 | O |
|
0.52 (0.36–0.77) | 30.6 (24.0–39.1) | 1.2 (0.83–1.9) | 59 | 2 |
| 22 | S |
|
0.15 (0.08–0.24) | 10.2 (5.6–18.3) | NTb | 68 | NCc |
| 23 | S |
|
0.45 (0.29–0.69) | 11.2 (4.4–27.9) | NTb | 25 | NCc |
| 24 | S |
|
0.7 (0.5–0.9) | 28.3 (12.4–49.5) | 82 (49.9–82.1) | 40 | 117 |
| 25 | S |
|
2.73 (1.9–3.8) | 23.3 (16.8–32.3) | NTb | 8 | NCc |
| 26 | S |
|
1.78 (1.5–2.1) | 11.8 (9.2–15.2) | NTb | 6 | NCc |
| 27 | O |
|
2.4 (2.1–2.5) | 34 (24.1–49.6) | 36 (32–37) | 14 | 15 |
| 28 | S |
|
0.26 (0.2–0.3) | 2.53 (1.4–4.3) | 66 (41–105) | 10 | 254 |
| 29 | S |
|
1.22 (0.6–2.2) | 23 (13–39) | >100d | 19 | NCc |
Values reported in parentheses are 95% confidence intervals.
a
Inhibitory activities were measured by the conversion of [3H]-L-arginine into [3H]-L-citrulline.
b
Not tested.
c
Not calculable.
d
Not active at the maximum test concentration of 100 μM.