Table 1.
Structures of Minodronate and Risedronate analogues with altered substituents and bone mineral affinity leading to the development of OX14 (10).
| Name | Structure | Inhibition FDPS (IC50, nM) | Inhibition GGPPS (IC50, nM) | Mineral affinity Retention time (min) |
|---|---|---|---|---|
| Minodronate (7) |
|
1.9 | 869 | 10.33 |
| Deshydroxy Minodronate OX8 (7a) |
|
2.6 | >30,000 | 6.6 |
| OX9 (7b) |
|
15.4 | >300,000 | 26.97 |
| OX14 (10) |
|
2.5 | 7345 | 6.17 |
| OX18 (7c) |
|
628 | 3100 | <3 |
| Minodronate phosphonocarboxylate (7d) |
|
>60,000 | No inhibition | NA |
| OX139 (7e) |
|
6.6 | 700,000 | 6.3 |
| Risedronate (5) |
|
5.7 | 5675.4 | 9.97 |
| Deshydroxy Risedronate (NE58043) (5a) |
|
34.3 | ~2000 | 5.8 |
| OX11 (5b) |
|
664 | NA | 4.6 |
| OX24 (5c) |
|
142 | >30,000 | 14.7 |
| Risedronate phosphonocarboxylate, NE10790 (5d) |
|
>250,000 | No inhibition | NA |
| OX78 (5e) |
|
5 | - | 9.17 |
| OX104 (5f) |
|
18 | ~327,000 | 5.9 |
| OX105 (5g) |
|
13 | >750,000 | 6.1 |
| OX111 (5h) |
|
21 | 120,000 | 6.3 |
| OX112 (5i) |
|
7.4 | >340,000 | 5.9 |