Table 2.

Physiochemical and in vitro ADME data for milestone compounds

		compound
property or assessment		1	2	4f
cLogP[a]		4.3	6.7	7.6
aqueous solubility (PBS buffer, pH 7.4, μM)[b]		> 274.3	62.3	9.6
PAMPA permeability (×10−6 cm/s)[d]		ND	< 1.9/7.6/120	0/1.6/49
microsomal stability, %[e]	mouse	ND	ND	55.5
	human	ND	ND	46.5
plasma stability, %[f]	mouse	ND	ND	97.4
	human	ND	ND	80.8
plasma protein binding, %[g]	1 μM	ND	ND	99.0
	10 μM	ND	ND	99.1

^[a]Data were calculated using CambridgeSoft ChemBioDraw Ultra 12.0

^[b]Kinetic solubility method

^[d]Pe, membrane permeability, measured using an in vitro model for the passive transport from the GI into the blood system. Donor pH 5.0/6.2/7.4; acceptor pH 7.4. Controls: verapamil-HCl (highly permeable): 138; corticosterone (moderately permeable): 15; theophylline (poorly permeable): < 0.3;

^[e]Percent parent remaining after 1 h;

^[f]Percent parent remaining after 3 h;

^[g]mouse species; ND = not determined.