Table 3.
Inhibition of [3H]MK-801 and [3H]ifenprodil binding to rat cortical membranes by pentamidine analogs with aliphatic linkers of increasing length, and with aromatic linkers
 | |||||||||
|---|---|---|---|---|---|---|---|---|---|
| X | Y | n | R | Ar | [3H]MK-801 | [3H]ifenprodil | |||
| IC50 ± SD (n) (µM) | Ratio | IC50 ± SD (n) | |||||||
| No spm | 30 µM spm | No spm | |||||||
| 34 | NH | CH2 | 0 | — | — | 2.01 ± 0.76 (6) | 50.7 ± 13.8 (5) | 30.2 ± 10.4 (5) | 0.76 ± 0.05 (3) |
| 39 | NH | CH2 | 1 | — | — | 10.0 ± 2.3 (3) | 148 (2) | 17.0 (2) | 77.7 (2) |
| 41 | NH | CH2 | 2 | — | — | 4.55 ± 1.74 (3) | 84.2 (2) | 17.2 (2) | n.d. |
| 7 | NH | CH2 | 3 | — | — | 3.10 ± 0.11 (3) | 42.3 ± 1.9 (3) | 13.7 ± 0.6 (3) | 20.6 ± 5.4 (3) |
| 42 | NH | CH2 | 4 | — | — | 4.37 ± 0.32 (3) | 23.9 (2) | 5.26 (2) | n.d. |
| 43 | NH | CH2 | 5 | — | — | 4.67 ± 0.38 (3) | 25.4 (2) | 5.37 (2) | n.d. |
| 44 | NH | CH2 | 6 | — | — | 7.26 (2) | 31.1 (2) | 4.37 (2) | n.d. |
| 45 | NH | CO | 3 | — | — | 230 ± 97 (4) | 675 ± 131 (3) | 2.81 ± 0.76 (3) | 54.5, 65.6 (2) |
| 46 | NH | CO | 4 | — | — | 165 ± 68 (3) | 437 (2) | 3.46 (2) | n.d. |
| 47 | NH | CO | 5 | — | — | >1000 | >1000 | n.d. | n.d. |
| 48 | NH | CO | 6 | — | — | 22.9 ± 6.7 (4) | 170 ± 15 (3) | 7.25 ± 1.95 (3) | n.d. |
| 49 | NH | CO | 7 | — | — | 26.5 ± 2.6 (3) | 111 ± 13 (3) | 4.25 ± 0.94 (3) | n.d. |
| 50 | NH | CO | 8 | — | — | 15.7 ± 2.2 (3) | 62.6 ± 4.8 (3) | 4.07 ± 0.96 (3) | n.d. |
| 51 | NH | CO | 10 | — | — | 9.63 ± 1.45 (3) | 27.7 ± 6.9 (3) | 2.98 ± 0.58 (3) | n.d. |
| 52 | CO | NH | 3 | — | — | >1000 | >1000 | n.d. | n.d. |
| 53 | CO | NH | 4 | — | — | >1000 | >1000 | n.d. | n.d. |
| 54 | CO | NH | 5 | — | — | 688 (2) | >1000 | n.d. | n.d. |
| 55 | CO | NH | 6 | — | — | 266 (2) | 1208 (2) | 4.59 (2) | n.d. |
| 56 | CH2 | O | — | H | 1,2-Ph | 2.19 ± 0.85 (5) | 18.4 ± 3.2 (4) | 10.1 ± 3.2 (4) | 7.29 ± 2.85 (4) |
| 57 | O | CH2 | — | H | 1,2-Ph | 1.46 ± 0.60 (4) | 5.54 ± 1.23 (3) | 4.00 ± 0.93 (3) | 1.42, 2.05 (2) |
| 58 | O | CH2 | — | H | 1,3-Ph | 0.79 ± 0.32 (4) | 6.70 ± 0.89 (4) | 9.04 ± 1.93 (4) | 3.97 ± 1.59 (3) |
| 59 | O | CH2 | — | H | 1,4-Ph | 5.24 ± 1.12 (4) | 25.7 ± 0.9 (3) | 5.25 ± 1.29 (3) | 10.8, 16.8 (2) |
| 60 | O | CO | — | H | 1,4-Ph | 10.8 ± 1.7 (3) | 46.6 (2) | 3.98 (2) | 38.6, 27.0 (2) |
| 61 | NH | CO | — | H | 1,3-Ph | 42.3 ± 6.8 (4) | 36.7 (2) | 0.97 (2) | n.d. |
| 62 | NH | CO | — | H | 1,4-Ph | 53.9 ± 2.4 (3) | 52.9 (2) | 0.96 (2) | n.d. |
| 63 | NH | CO | — | H | 2,5-Fur | 152 ± 10 (3) | 153 ± 7 (3) | 1.01 ± 0.02 (3) | n.d. |
| 64 | NH | CO | — | i-Pr | 2,5-Fur | 10.6 ± 1.3 (3) | 174 ± 45 (3) | 16.9 ± 6.0 (3) | n.d. |
| 65 | NH | CO | — | H | 2,6-Pyr | 58.2 (2) | 70.9 (2) | 1.22 (2) | >100 |
| 66 | NH | CO | — | i-Pr | 2,6-Pyr | 6.94 ± 1.22 (3) | 74.9 ± 13.5 (3) | 10.8 ± 1.2 (3) | 50.1, 49.4 (2) |
| 67 | CO | NH | — | H | 2,6-Pyr | 125 (2) | 233 (2) | 1.85 (2) | n.d. |
Definitions as in caption to Table 1;
Fur, furandiyl; Pyr, pyridinediyl.