Physicochemical properties of abemaciclib and palbociclib

Chemical structureEmbedded ImageEmbedded Image
Molecular mass (Da)507448
clogPa4.3 (3.36)b2.8 (2.29)
cpKaa8.4 (7.9)8.9 (8.4)
logD (pH 6)c(1.39)(−0.12)
clogD (pH 7.4)a3.4 (2.70)1.3 (1.25)
Polar surface area (Å2)a75105
H-bond donor number12
H-bond acceptor number89
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.