Table 3.

Optimization of subunit selectivity through evaluation of Ring C substituents.

Number	R1	R2	R7	R8	R9	R10	NR2A IC50	NR2B IC50	NR2C IC50	NR2D IC50	GluR1 IC50	NR2Aa NR2D	GluR1b NR2D
36		NO2	Cl				>300	110	22	14	>300	>20	>20
37		NO2		Cl			16	13	2	1	7	16	7
38		NO2			Cl		32	52	16	15	41	2	3
39 *		NO2				Cl	56	243	12	9	87	6	10
40		NO2		Cl		Cl	224	109	16	10	>300	22	30
41	NO2			Cl		Cl	>300	>300	9	6	>300	>50	>50
2		NO2		H			21	30	12	9	32	2	4
42		NO2		F			36	33	14	7	7	5	1
37		NO2		Cl			16	13	2	1	7	16	7
43		NO2		Br			17	13	2	1	8	17	8
44		NO2		I			18	6	1	0.6	31	18 d	52
45		NO2		CH3			12	15	5	2	27	6	14
46 *		NO2		OCH3			229	>300	6	3	>300	76	>100
47 *		NO2		NO2			NE	NE	204	90	>300	-	-
48		NO2		OH			237	>300	43	10	96	24	10
49		NO2		C6H5			11	3	2 c	2 c	5	6	3
50		NO2		R8-C4H4-R9			11	5	2 c	2 c	4	6	2
51		NO2		R8-OCH2CH2O-R9			>300	>300	281	213	>300	1	1
52		NO2		R8-OCH2O-R9			112	162	40	36	>300	3	>8
53 *		NO2		CH(CH3)2			101	98	6	7	200	14	29
54		NO2		CH2CH2CH3			28	18	3	4	50	7	13
55		NO2		2-thiophene			157	129	5	3	280	52	93
56		NO2		CHCHC6H5			19	30	4	4	131	5	33

IC₅₀ values in μM were determined by fitting the Hill equation to average composite concentration-effect curves from 7-26 oocytes injected with NR1/NR2A, NR1/NR2B, NR1/NR2C, NR1/NR2D, GluR1 cRNA. Oocytes were obtained from 2-5 frogs. Compound 2, previously shown in Table 1, is included to facilitate comparison. IC₅₀ values greater than 300 μM were determined as described in Experimental Methods. NE indicates no effect.

^a(IC₅₀ NR2A)/(IC₅₀ NR2D)

^b(IC₅₀ GluR1)/(IC₅₀ NR2D)

^cdata were fitted with a variable minimum (see text)

^dselectivity was calculated from IC₅₀ values rounded to nearest value in μM.

^*1-10 mM 2-hydroxypropyl-β-cyclodextrin was included for 30 and/or 100 μM concentrations of test compound. See Figure S2 (Supporting Information) for full general structure.