. Author manuscript; available in PMC: 2019 Mar 28.

Published in final edited form as: J Med Chem. 2019 Feb 13;62(4):1761–1780. doi: 10.1021/acs.jmedchem.8b01679

Table 9.

Additional ADMET Properties of 47, 49, 58, and 62^a

		47	49	58	62
Plasma protein binding (% bound)	human	92.4	94.8	93.4	97.3
	rat	ND	94.3	91.5	ND
	dog	ND	96.3	91.5	ND
Binding in rat brain homogenate (2μM) (% bound)		ND	ND	98.4	ND
MDCK-MDR1 cell line (P-gp)	A-B (10⁻⁶ cm/s)	8.76	13.5	7.1	4.6
MDCK-MDR1 cell line (P-gp)	Efflux ratio	1.5	0.896	2.3	5.2
Caco-2 cell line	A-B (10⁻⁶ cm/s)	19.2	ND	20.9	ND
Caco-2 cell line	Efflux ratio	0.493	ND	0.38	ND
Solubility (μM) at pH 7.4		75	84	74	70

KOR-antagonists were used as monotartrate salts. ND = No data. A-B = movement of the compound from the apical to the basal side of the membrane; a surrogate for permeability.