Table 4.

Substitutions for Ring B carboxylic acid and Ring A nitro groups.

Number	R1	R2	R4	R8	NR2A IC50	NR2B IC50	NR2C IC50	NR2D IC50	GluR1 IC50	NR2Aa NR2D	GluR1b NR2D
57 *		NO2			>300	>300	>300	>300	>300	1	1
46 *		NO2	COOH	OCH3	229	>300	6	3	>300	76	>100
58		NO2	CN	OCH3	>300	>300	>300	>300	>300	1	1
59		NO2	CONH2	OCH3	>300	82	58	>300	>300	1	1
60		NO2	COOCH3	OCH3	218	46	39	38	138	6	4
61		OCH3	COOH	OCH3	73	109	18	9	220	8	24
62		COOH	COOH	OCH3	>300	>300	>300	131	>300	>2	>2
63		COOCH3	COOH	OCH3	80	39	15	6	41	13	7
64	COOCH3	COOCH3	COOH	OCH3	>300	>300	124	52	>300	>6	>6
7	NO2		COOH		64	93	15	15	>300	4	>20
65	SCH3		COOH		211	79	42	22	244	10	11
66	CN		COOH		94	106	28	34	>300	3	>9
67	N(CH3)2		COOH		>300	>300	63	53	>300	>5	>5
68	OCHF2		COOH		73	89	33	22	208	3	9
69	OCH2CHCH2		COOH		>300	144	111	30	>300	>10	>10
70	OCH2COOH		COOH		>300	>300	>300	>300	>300	1	1
71	COOH		COOH		>300	>300	>300	>300	>300	1	1

IC₅₀ values in μM were determined by fitting the Hill equation to average composite concentration-effect curves from 4-26 oocytes injected with NR1/NR2A, NR1/NR2B, NR1/NR2C, NR1/NR2D, GluR1 cRNA. Oocytes were obtained from 1-4 frogs. Compounds 7 and 46, previously shown in Table 3, are included to facilitate comparison. IC₅₀ values greater than 300 μM were determined as described in the Experimental Methods.

^a(IC₅₀ NR2A)/(IC₅₀ NR2D)

^b(IC₅₀ GluR1)/(IC₅₀ NR2D)

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