Table 3. Reactive Metabolite SAR for Analogs of Compound 3.

Cmpd	X	R	GluA1/γ-8 pIC50a	GSH adductb	cLogP
3	NH	H	8.3 ± 0.31	yes	4.1
14	O	H	5.6 (n = 1)	yes	4.1
15	S	H	8.6 ± 0.3	yes	4.7
16	CH2	H	7.8 ± 0.2	no	3.6
17	CH2	F	8.6 ± 0.3	no	4.1
18	CH2	CH3	9.7 ± 0.3	no	4.2

^apIC₅₀ measured in a FLIPR assay using HEK-293 cells expressing a human GluA1o-γ-8 fusion construct; unless noted, all data are the result of at least three assays run in triplicate with the mean value and standard deviation reported.

^bCompounds were incubated for 1 h in human liver microsomes supplemented with glutathione (GSH) and NADPH.