Table 5. Oxygen-Tethered TSPO Ligands Based on 15a: Dependence of Binding Affinity, Lipophilicity, and Genotype Sensitivity on Scaffold Aryl Groups.

ligand	Ar	A	B	C	D	E	rat Ki (nM)a	cLogD	LipE	LAB Ki (nM)b	HAB Ki (nM)c	(LAB Ki)/(HAB Ki)
15a	Ph	CH	CH	CH	CH	CH	0.070 ± 0.004	4.73	5.42 ± 0.03	1.3 ± 0.2	0.5 ± 0.2	2.5 ± 0.9
15b	H	CH	CH	CH	CH	CH	5.7 ± 0.5	2.96	5.29 ± 0.04	66 ± 22	3.3 ± 0.9	20 ± 9
15c	Ph	H			H	CH	3.3 ± 0.6	3.52	5.3 ± 0.3	62 ± 11	2.0 ± 0.6	31 ± 11
19a	Ph	N	CH	CH	CH	CH	1.4 ± 0.5	4.27	4.6 ± 0.1	23 ± 7	1.1 ± 0.3	21 ± 8
19b	Ph	CH	N	CH	CH	CH	0.6 ± 0.1	4.15	5.0 ± 0.1	25 ± 8	1.3 ± 0.5	19 ± 9
19c	Ph	CH	CH	N	CH	CH	0.3 ± 0.2	4.15	5.4 ± 0.3	47 ± 26	1.4 ± 0.4	33 ± 20
19d	Ph	CH	CH	CH	N	CH	0.29 ± 0.03	3.91	5.63 ± 0.04	4.7 ± 0.7	0.9 ± 0.2	5 ± 2
19e	Ph	CH	CH	CH	CH	N	0.13 ± 0.08	5.66	4.4 ± 0.5	2 ± 1	2 ± 1	1 ± 1
22a	o-Py	CH	CH	CH	CH	CH	0.10 ± 0.05	4.18	5.9 ± 0.2	1.4 ± 0.5	1.4 ± 0.2	1.0 ± 0.4
22b	m-Py	CH	CH	CH	CH	CH	0.20 ± 0.03	4.06	5.6 ± 0.1	12 ± 3	0.90 ± 0.09	13 ± 4
22c	p-Py	CH	CH	CH	CH	CH	0.22 ± 0.02	4.06	5.60 ± 0.04	7 ± 3	1.0 ± 0.5	7 ± 5

^aMean ± SD for n = 6, except for 19d, 22b (n = 5).

^bMean ± SD for n = 6, except for 15a,b, 19c (n = 5), and 15c (n = 4).

^cMean ± SD for n = 6, except for 15c (n = 5).