. Author manuscript; available in PMC: 2023 Feb 15.

Published in final edited form as: Bioorg Med Chem Lett. 2021 Dec 31;58:128518. doi: 10.1016/j.bmcl.2021.128518

Table 7.

A, ADME test results for Urea 61 with non-planar and electron-deficient octahydroquinolin-4(1H)-one core; B, PK profile of urea 61 via IV and PO routes.

A	Cmpd	Solubility (μM)		Metabolic stability (T_1/2, min)		CYP (#/9 of isoforms, > 50% of inhibition at 10 μM)	Plasma Protein Binding		Caco-2 Permeability^*
	Cmpd	PH = 4	PH = 7	Human	Mouse	CYP (#/9 of isoforms, > 50% of inhibition at 10 μM)	Mouse (%)	Human (%)	P_app(a-b) 10⁻⁶ cm/s	P_app(b-a) 10⁻⁶ cm/s	Efflux Ratio
	10 (38017)			1.7	6.6
	61	239	253	71	56	1 (2C19, 56%)	94	90	14.7	7.8	0.5
B	IV (3 mg/kg)				PO (10 mg/kg)
	Cl_obs (mL/min/kg)	T_1/2 (hr)	AUC_last (h*ng/mL)	Vss_obs (L/kg)	T_1/2 (hr)	C_max (ng/mL)	AUC_last (h*ng/mL)	F (%)
	25.5	0.6	1952	0.8	0.7	2727	4516	69

the Caco-2 data were from a test for racemic 58.