Table 1. Calculated and Experimental Properties of Test Compounds.

^aKinetic solubility in aqueous phosphate buffer (pH 7.4) determined by LC/MS after 24 h of incubation (experiment run by Analyza).

^bDistribution coefficient between n-octanol and aqueous buffer (pH 7.4) determined by LC/MS (experiment run by WuXi AppTech).

^cCalculated values using ChemAxon.¹⁰

^dEffective permeability (PAMPA assay run by Analyza).

^eMembrane retention.

^fLog of the apparent permeability coefficient.

^gpK_a values determined by capillary electrophoresis; for diprotic compounds, the second equivalence point is indicated in brackets (experiment run by Analyza).

^hPlasma protein binding, fraction unbound (fu) determined by equilibrium dialysis.

^*The X-ray crystal structure revealing the H-bond pattern is shown in the Supporting Information.

^†The permeability value could not be calculated, as the concentration of test compound in the acceptor plate was below the limit of quantitation (<LOQ).

^‡Compound precipitated in donor plate.

^#Compound appeared to exhibit high nonspecific binding.

^§Compound appeared to be unstable during the 24 h incubation time of the assay; ND = not determined.