Table 1.
Novel phosphate and phosphonate analogues: structure and effects on in vivo heart function after subcutaneous infusion for 28 days as determined by echocardiography-derived FS in the LAD ligation model of ischemic heart failure in mice.
| Compound or condition |
Structure | FS in %a | n = | Corresponds to compound: |
|---|---|---|---|---|
| Vehicle control | - | 17.33 ± 1.36 | 10 | - |
| P2X4R transgenic mouse | - | 23.69 ± 1.74* | 9 | - |
| Charged nucleotides | ||||
| 1 |  |
22.14 ± 0.68* | 20 | - |
| 4 |  |
23.06 ± 1.14* | 18 | 1 (deuterated) |
| 5 |  |
ND | 1 (thio) | |
| 6 |  |
ND | 1 (phosphonate, 2-iodo) | |
| Masked nucleotides | Ester derivative of: | |||
| 7 |  |
24.71 ± 1.42* | 8 | 1 |
| 8 |  |
25.77 ± 1.10* | 8 | 1 |
| 9 |  |
24.07 ± 1.64* | 11 | 1 |
| 10 |  |
21.48 ± 1.38 | 8 | 4 |
| 11 |  |
24.31 ± 1.45* | 13 | 5 |
| 12 |  |
ND | 1 (thio) | |
| 13 |  |
24.76 ± 1.32* | 12 | 5 (dithio) |
| 14 |  |
ND | 2 | |
| 15 |  |
23.05 ± 1.45* | 11 | 6 |
| 16 |  |
ND | 3 | |
a
at 10 µM, expressed as mean ± SEM.
*
P<0.05 vs. vehicle for all compounds tested, except compound 10, which displayed P<0.1.
ND – not determined.