Table 1.

Lipophilicity and Pharmacological Data^[a] of Compounds 2, 4, 5, 7–16, 29, 32.

	logP		CB1[b,c]	CB2[c,d]
compd	Calcd[e]	Exp[f]	Ki[g] (nM)	Ki (nM)	S.I.[h]
2[23]	6.41	6.40	>10000	0.7 ± 0.2	>14285
4	7.78	8.08	NTi	NT	-
5	6.92	7.78	> 10000	1680.0 ± 24.5	> 6
7	8.33	7.71	> 10000	> 10000	-
8	5.15	5.83	> 10000	32.2 ± 1.2	> 284
9	5.53	5.15	> 10000	250.0 ± 8.6	> 40
10	6.56	5.77	207.5 ± 5.5	2.7 ± 0.8	76
11	5.55	5.18	> 10000	1.2 ± 0.2	> 8620
12	5.93	5.26	> 10000	6.5 ± 2.2	> 1543
13	6.96	6.38	33.0 ± 0.6	0.4 ± 0.1	82
14[22]	6.01	6.44	996. 0± 12.1	14.3 ± 2.1	69
15	5.81	-	321.9 ±2.1	11.1 ± 3.6	29
16	6.65	-	3414.6 ± 9.8	12.6 ± 4.3	271
29	3.39	-	> 10000	> 10000	-
32	3.35	-	> 10000	190.0 ± 10.0	> 52
SR144528[j,k]	-	-	>2820	5.4 ± 1.3	>522
Rimonabant[j,l]	-	-	12.0 ± 8.3	790.0 ± 11.2	0.015

^[a] Data represent mean values +/− SD for at least three separate experiments performed in duplicate and are expressed as K_i (nM).

^[b] CB1: human cannabinoid type 1 receptor.

^[c] For both receptor binding assays, the new compounds were tested using membranes from HEK cells transfected with either the CB1 or CB2 receptor and [³H]-(−)-cis-3-[2-hydroxy-4-(1,1-dimethylheptyl)-phenyl]-trans-4-(3-hydroxy-propyl)-cyclohexanol ([³H]CP-55,940).

^[d] CB2: human cannabinoid type 2 receptor.

^[e] Calculated as clogP using the software ChemDraw Ultra 8.0 of CambridgeSoft Corporation (Cambridge, MA).

^[f] Determined by HPLC using a Lichrocart 125-4 Lichrospher 100 RP-18 (5 μm) column and MeOH/H₂O mixtures as the eluent.

^[g] K_i: “Equilibrium dissociation constant”, that is the concentration of the competing ligand that will bind to half the binding sites at equilibrium, in the absence of radioligand or other competitors.

^[h] S.I.: selectivity index for CB2, calculated as K_i(CB1)/K_i(CB2) ratio.

^[i] NT, not tested because of solubility problems.

^[j] The binding affinities of reference compounds were evaluated in parallel with the test compounds under the same conditions.

^[k] CB2 reference compound.

^[l] CB1 reference compound.