Table 2.
Physicochemical Properties of Inhibitors 1–3 and Fragments 5–17
| Inhibitors | |||
|---|---|---|---|
| Properties (Ro5) | 1 | 2 | 3 |
| MW (≤500 Da) | 401 | 419 | 410 |
| cLogP (≤5) | 0.14 | 2.06 | −0.05 |
| HBD (≤5) | 2 | 2 | 2 |
| HBA (≤10) | 7 | 5 | 7 |
| Rot. bonds (≤5) | 5 | 5 | 5 |
| Ro5 compliant | ✓ | ✓ | ✓ |
| NMR | ✓ | ✓ | ✓ |
| DSF | ✓ | ✓ | ✓ |
| ITC | ✓ | ✓ | ✓ |
| FP | ✓ | ✓ | ✓ |
| Fragments | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Properties (Ro3) | 13 | 5 | 6 | 7 | 8 | 9 | 10 | 11 | 12 | 14 | 15 | 16 | 17 |
| NHA | 13 | 13 | 10 | 12 | 15 | 14 | 17 | 13 | 16 | 19 | 19 | 23 | 25 |
| MW (≤300Da) | 186 | 182 | 141 | 165 | 207 | 183 | 225 | 174 | 216 | 262 | 267 | 320 | 343 |
| cLogP (≤3) | −1.84 | −0.22 | −0.34 | 1.06 | 0.92 | 2.98 | 2.84 | 0.87 | 0.73 | 0.04 | −1.71 | 0.01 | 0.17 |
| HBD (≤3) | 2 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 1 | 2 | 2 | 2 | 2 |
| HBA (≤3) | 3 | 2 | 3 | 2 | 2 | 1 | 1 | 1 | 2 | 3 | 5 | 5 | 5 |
| Rot. bonds (≤3) | 0a | 3 | 2 | 2b | 3b | 2 | 3 | 2 | 3 | 2a | 2a | 4a | 4a |
| PSA (≤60) | 69.6 | 50.7 | 64.7 | 52.3 | 55.4 | 26.0 | 29.1 | 47.6 | 50.7 | 69.6 | 91.2 | 95.9 | 91.2 |
| Ro3 compliant | ✓ c | ✓ | ✓ c | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ | ✓ c | ✗ | ✗ | ✗ |
| NMR | ✗ | ✗ | ✗ | ✗ | ✗ | ✗ | ✗ | ✗ | ✗ | ✓ | ✓ | ✓ | ✓ |
| DSF | ✗ | ✗ | ✗ | ✗ | ✗ | ✗ | ✗ | ✗ | ✗ | ✗ | ✓ | ✓ | ✓ |
| FP | ✗ | ✗ | ✗ | ✗ | ✗ | ✗ | ✗ | ✗ | ✗ | ✗ | ✓ | ✓ | ✓ |
| ITC | ✗ | - | - | - | - | - | - | - | - | - | ✓ | ✓ | ✓ |
✓, yes or true;
✗, not or false.
a
The C(α)–C(O) bond of the Hyp core, about which rotation is described by the Ramachandran ψ dihedral angle, was not counted as a rotatable bond.
b
The C(α)–O bond of the methyl ester was not counted as a rotatable bond.
c
Not considering the requirement for PSA.