Table 1.

σ₁ and σ₂ receptor affinity of synthesized piperidines and some lead and reference compounds.

Compd	R1	NR2	K i±SEM [nM] (n=3)		σ1 : σ2
			σ1	σ2	selectivity
136	1,3‐dioxane[a]	NHCH2Ph	6.0±1.0	4200	14
237	tetrahydropyran[a]	NHCH2Ph	1.6±0.2	378	236
338	cyclohexane[a]	NHCH2Ph	0.61±0.1	49±31	80
4a	H	NHCH2Ph	165	372	2.3
4b	H	NH(CH2)3Ph	849	0 %[b]	–
13a	Ts	NHCH2Ph	57±21	763	13
13b	Ts	NH(CH2)3Ph	291±139	567	2
18a	CH3	NHCH2Ph	7.9±0.2	483	61
18b	CH2CH3	NHCH2Ph	129±38	131	1
19a	CH3	NH(CH2)3Ph	50±17	0 %[b]	>20
19b	CH2CH3	NH(CH2)3Ph	2400	334	0,14
20a	CH3	NHCH2C6H11	16±5	285	18
21a	CH3	N(CH3)CH2Ph	19±9	77±5	4
22a	CH3		27±11	1600	59
(+)‐pentazocine		–	5.4±0.5	–	–
haloperidol		–	6.6±0.9	125±33	19
di‐o‐tolylguanidine		–	71±7.9	54±8	0.76

[a] Structures of compounds 1–3 are shown in Figure 1. [b] For compounds with low affinity the inhibition (in %) of radioligand binding at a test compound concentration of 1 μM is given. The piperidines were tested as mixtures of cis‐ and trans‐configured diastereomers. cis : trans=60 : 40 to 85 : 15.