Table 2.

Bioactivities of 4-anilidopiperidine analogues at the δ and μ opioid receptors¹⁰

Compound	n	R1	R2	Ar	Binding Kia (μM)		Bioassay IC50b (μM)
					hDOR (δ)	rMOR(μ)	MVD(δ)	GPI(μ)
1	1	(S) NH2	(S) Me	2,6-Dimethyl-4-hydroxyphenyl	1.7	0.50	39% at 1 μMc	3% at 1 μMc
2	1	(S) NH2	(R) Me	2,6-Dimethyl-4-hydroxyphenyl	0.26	0.30	13% at 1 μMc	3.3
3	1	(S) NH2	H	2,6-Dimethyl-4-hydroxyphenyl	0.050	0.047	2% at 1 μMc	45% at 30 μMc
4	1	(S) NH2	H	4-Hydroxy phenyl	16	7.9	18% at 1 μMc	8% at 1 μMc
5	1	(S) NH2	H	Ph	6.9	3.9	0% at 1 μMc	2% at 1 μMc
6	1	(R) NH2	H	4-Chlorophenyl	nc	6.9	28% at 1 μMc	0% at 1 μMc
7	1	(S) NH2	H	4-Thiazoyl	76	9.7	8% at 1 μMc	3% at 1 μMc
8	1	(S) NH2	H	3-Benzothiopheneyl	15	2.6	0% at 10 μMc	28% at 10 μMc
9	1	(S) NH2	H	2-Naphthyl	3.3	1.1	26% at 1 μMc	8% at 1 μMc
10	1	(S) NH2	Ph	Ph	6.5	0.40	48% at 10 μMc	73% at 10 μMc
11	1	H	NH2	4-Chlorophenyl	2.4	0.99	12% at 1 μMc	5% at 1 μMc
12	1	H	NH2	4-Methylphenyl	2.9	3.0	27% at 10 μMc	24% at 10 μMc
13	1	H	NH2	4-Methoxyphenyl	9.0	9.7	19% at 1 μMc	3% at 1 μMc
14	1	H	H	3-Bromophenyl	12	1.9	0% at 1 μMc	18% at 1 μMc
15	1	H	H	3-Chloro-4-methoxyphenyl	6.3	3.8	0% at 1 μMc	33% at 10 μMc
16	0	(S) NH2		Ph	nc	6.4	7% at 1 μMc	3% at 1 μMc
17	0	(R) NH2		Ph	nc	5.1	12% at 1 μMc	1% at 1 μMc
18	0	(S) NH2		2-Indanyl	15	2.6	19% at 10 μMc	59% at 10 μMc
	(2S,3R)-Tmt-Tic11				0.0093	35	547-fold shift at 1 μM	30% at 30 μMc
	Fentanyl12				0.57	0.0059	—	5.2
	Dmt-Tic13				0.00097	0.0046	38.9ED50	500ED50

^aCompetition analyses against radiolabeled ligand ([³H]DPDPE for δ, [³H]DAMGO for μ) were carried out using membrane preparations from transfected HN9.10 cells that constitutively express the respective receptor types.

^bConcentration at 50% inhibition of muscle contraction at electrically stimulated isolated tissues.

^cInhibition % of muscle contraction at electrically stimulated isolated tissues. nc: no competition at 10⁻⁵ M.