Table 3.

Inhibitions of [³H]TCP binding at the PCP site of the NMDA receptor (%), binding affinities (K_i), and clogD values for N-1-naphthyl-N’-(3-substituted-phenyl)-N’-methylguanidines and compound 30.

Ligand	X	Y	Inhibition (%)a	[3H]TCP Ki (nM)b	cLogDc
14	F	H	36.9		1.80
15	Cl	H	69.2		2.23
16	Br	H	104	53.7	2.40
17	CN	H	62.9		1.13
18	OH	H	11.9		0.83
19	N(Me)2	H	94.6	36.7	2.07
20	CF3	H	107	18.3	2.23
21	OCF3	H	79.2		2.49
22	SCF3	H	80.0	447	2.98
23	OCF2H	H	66.4		1.80
24	Ac	H	82.3	152	1.07
25	CH=CH2	H	73.9		2.38
26	CH≡CH	H	74.3		1.61
27	CH2OH	H	20.0		0.81
28	SCH2CH2F	H	76.7		2.40
29	SCH=CH2	H	88.4		2.04
30	d		55.0		4.15
31	OPh	H	30.0		3.33
32	Bn	H	16.2		3.52
33	OBn	H	–2.5		3.52
34	Cl	2-F	84.0	701	2.20
35	Cl	4-F	65.8		2.35
36	Cl	5-F	86.8	78.4	2.06
37	Cl	2,6-F	37.6		2.33
38	Br	4-F	56.5		2.29
39	Br	6-F	13.8		2.13
40	CN	4-F	62.1		1.02
41	Me	4-F	46.5		1.77
42	OMe	5-F	32.9		1.48
43	NO2	4-F	0.7		1.35

^aAt 1.0 μM concentration. Mean from two experiments.

^bBinding affinities were measured for compounds having inhibition ≥ 80%, except for 29. Mean from two experiments.

^cCalculated with ACD Labs program.

^dThis compound has 2-naphthyl as the N’-aryl group.