. Author manuscript; available in PMC: 2019 Nov 8.

Published in final edited form as: J Med Chem. 2018 Oct 19;61(21):9647–9665. doi: 10.1021/acs.jmedchem.8b01126

Table 4.

Mouse Brain Exposure of 5,7-substituted 8-hydroxyquinolines at one hour

Example	P-gp ER^a	Plasma Protein Binding^b	Brain Tissue Binding^c	Mouse Brain Penetration^d
Example	P-gp ER^a	Plasma Protein Binding^b	Brain Tissue Binding^c	Total Brain (ng/g)	Total Plasma (ng/ml)
11	NT	0.5 (r)	2.9	blq	173
12	NT	3.3 (m)	4.4	10.5	68
15	NT	6.9 (m)	10.3	11	250
16	NT	0.5 (m)	0.5	109	235
17	NT	1.4 (m)	NT	BLQ	3538
18	1.1	0.6 (r)	3.6	1094	2542
19	0.8	0.5 (r)	2.6	5655	16650
20	0.7	1.2 (r)	2.4	527	5720
21	NT	1.2 (r)	1.39	518	1744
22	1.1	0.84 (m)	0.5	1686	9780
25	0.5	0.2 (r)	4.2	1914	6160
26	NT	0.5 (r)	1.6	2792	14669
28	1.2	0.6 (r)	8	110	1819
29	0.4	0.5 (r)	3.4	1154	16250
30	NT	0.5 (m)	1.8	55	576

A:B/B:A efflux ratio from P-glycoprotein expressing MDCK cells. NT=not tested.

Percent free from either mouse (m) or rat (r) plasma as measured by equilibrium dialysis.

Percent free from rat brain tissue.

Total brain and total plasma concentrations 1 hour after ip dosing 10mg/kg to 2 mice.