Table 5.

Optimization of Ring A, Ring B, Ring substituents.

Number	R1	R2	R4	R5	R8	NR2A IC50	NR2B IC50	NR2C IC50	NR2D IC50	GluR1 IC50	NR2Aa NR2D	GluR1b NR2D
72 *	NO2		COOH		I	>300	>300	2 c	1 c	>300	>150	>220
44		NO2	COOH		I	18	6	1	0.6	31	30	52
73	NO2			COOH	I	>300	279	9	8	>300	>37	>37
74		NO2		COOH	I	8	11	2	1	21	8	21
75	NO2		COOH		OCH3	197	206	13	7	>300	28	>42
46 *		NO2	COOH		OCH3	229	>300	6	3	>300	76	>100
76	NO2			COOH	OCH3	238	238	21	16	>300	15	>19
77		NO2		COOH	OCH3	208	>300	24	13	289	16	22

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. Compounds 44 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)

^cindicates data fitted with variable minimum (see Fig 2B).

^*1 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.