Table 1.

Radioligand Competition Binding Affinity(K_i)Data of PAM Derivatives

compd	R1	R2	MW	cLogP	Ki (CB2), nMa,b	Ki (CB1, nMa,c	SId
9	H	p-(CH3)2N-	401.50	4.04	777	>20000	>26
11	H	H-	358.43	3.93	9930	NT
12	H	o-F-	376.42	4.08	35330	NT
13	H	m-F-	376.42	4.08	12670	NT
14	H	p-F-	376.42	4.08	10900	NT
15	H	p-Cl-	392.88	4.54	3081	NT
16	H	p-Br-	437.33	4.70	2226	NT
17	H	p-CH3-	372.46	4.45	494	109
18	H	p-i-C3H7-	400.51	5.18	85	>20000	>235
19	H	p-CH3O-	388.46	3.78	783	>20000	>26
20	H	p-C2HsO-	402.49	4.13	1500	NT
21	H	p-i-C3H7O-	416.51	4.55	313	>20000	>64
22	H	o-CF3-	426.43	4.81	11780	NT
23	H	p-CF3-	426.43	4.81	596	>20000	>34
24	H	p-NO2	403.43	3.87	NB	NT
25	H	p-H2N-	373.45	2.51	12550	NT
26	H	p-(C2H5)2N-	429.55	4.76	64	>20000	>313
27	H	p-(C3H7)2N-	457.61	5.80	22	>20000	>909
28	H	p-(C4H9)2N-	485.66	6.69	221	>20000	>90
29	H	p-(benzyl)2N-	553.69	7.33	203	>20000	>99
30	H	p-pyrrolidinyl-	427.53	4.45	71	>20000	>281
31	H	p-piperidyl-	441.56	4.89	595	>20000	>34
32	Cl	H-	427.32	5.14	NB	NT
33	Cl	o-F-	445.31	5.29	10850	NT
34	Cl	p-F-	445.31	5.29	NB	NT
35	Cl	p-Cl-	461.77	5.75	154	>20000	>130
36	Cl	p-CH3-	441.35	5.66	462	>20000	>43
37	Cl	p-CH3O-	457.35	4.98	310	>20000	>65
38	Cl	o-CF3-	495.32	6.02	158	>20000	>127
39	Cl	p-CF3-	495.32	6.02	101	>20000	>198
40	Cl	p-NO2-	472.32	5.08	NB	NT
41	CF3	H-	494.43	5.69	NB	NT
42	CF3	o-F-	512.42	5.83	NB	NT
43	CF3	p-F-	512.42	5.83	NB	NT
44	CF3	p-Cl-	528.87	6.29	NB	NT
45	CF3	p-CH3-	508.46	6.20	NB	NT
46	CF3	p-CH3O-	524.45	5.53	NB	NT
47	CF3	p-CF3-	562.43	6.57	NB	NT
1e,f					2.1	NT
10e,g					NT	10.6

^aBinding affinities of compounds for CB₁ and CB₂ receptor were evaluated using [³H]CP-55,940 radioligand competition binding assay.

^bNB: no binding, K_i > 20000 nM.

^CNT: not tested.

^dSI: selectivity index for CB₂, calculated as K_i(CB₁)/K_i(CB₂) ratio.

^eThe binding affinities of reference compounds were evaluated in parallel with compounds 9, 11–61 under the same conditions.

^fCB₂ reference compound SR144528.

^gCB₁ reference compound SR141716.