Physicochemical properties of abemaciclib and palbociclib
| Property | Abemaciclib | Palbociclib |
|---|---|---|
| Chemical structure |  |  |
| Molecular mass (Da) | 507 | 448 |
| clogPa | 4.3 (3.36)b | 2.8 (2.29) |
| cpKaa | 8.4 (7.9) | 8.9 (8.4) |
| logD (pH 6)c | (1.39) | (−0.12) |
| clogD (pH 7.4)a | 3.4 (2.70) | 1.3 (1.25) |
| Polar surface area (Å2)a | 75 | 105 |
| H-bond donor number | 1 | 2 |
| H-bond acceptor number | 8 | 9 |
| Aqueous solubility (mg/ml)d | >2 at pH 4.5; 0.012 at pH 7.5 | >2 at pH 2.0; 0.033 at pH 7.6 |
↵a Calculated log octanol-water partition coefficient (clogP), calculated negative logarithm of the acid dissociation constant (cpKa), and calculated log octanol-water partition coefficient at a specific pH (clogD) were obtained using ChemAxon software (Cambridge, MA). Polar surface area was obtained from a Novartis (Basel, Switzerland) version of a prediction algorithm that estimates the sum of the molecular surface area contributed by N, O atoms, and/or H atom bonded with N or O in a molecule.
↵b All values in parentheses are measured.
↵c logP and logD were measured using an automated potentiometric method (Sirius Analytical, East Sussex, UK).
↵d Solubility was measured at equilibrium in phosphate buffer.