. Author manuscript; available in PMC: 2011 Aug 12.

Published in final edited form as: J Med Chem. 2010 Aug 12;53(15):5476–5490. doi: 10.1021/jm100027p

Table 7.

Optimization of Ring B substituents for pyridinyl analogues.



Number	R₄	R₅	R₆	R₈	NR2A IC₅₀	NR2B IC₅₀	NR2C IC₅₀	NR2D IC₅₀	GluR1 IC₅₀	IC₅₀NR2A IC₅₀NR2D	IC₅₀GluR1 IC₅₀NR2D
87					40	51	140	35	74	1	2
88				I	132	>300	>300	108	>300	1	3
89 *	OCH₃			I	>300	>300	>300	>300	>300	1	1
90 *		OCH₃		I	>300	>300	>300	200	>300	1	1
91 *			OCH₃	I	31	30	3	3	199	10	66
92 *	CH3			I	>300	>300	>300	>300	>300	1	1
93 *		CH3		I	>300	>300	241	>300	>300	1	1
94 *			CH3	I	>300	156	70	25	83	12	3
95 *	NO2			I	>300	>300	204	218	>300	1	1
96 *		NO2		I	>300	>300	>300	>300	>300	1	1
97 *			NO2	I	206	105	19	5	>300	41	60
98	COOH			I	26	31	6	4	61	7	15
99		COOH		I	45	49	7	4	64	11	16

IC₅₀ values in μM were determined by fitting the Hill equation to average composite concentration-effect curves from 3-20 oocytes injected with NR1/NR2A, NR1/NR2B, NR1/NR2C, NR1/NR2D, GluR1 cRNA. Oocytes were obtained from 1-3 frogs. IC₅₀ values greater than 300 μM were determined as described in the Experimental Methods. 1-10 mM 2-hydroxypropyl-β-cyclodextrin was included for 10, 30, and/or 100 μM concentrations of test compounds. See Figure S2 (Supporting Information) for full general structure.