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. 2020 Jun 6;25(11):2640. doi: 10.3390/molecules25112640

Table 1.

Opioid Receptor Binding Data a (Ki, nM) and Stimulation of [35S]GTPγS b Binding at MOR (μ), DOR (δ) and KOR (κ) opioid receptors.

Receptor Binding (Ki, nM) [35S]GTPγS
Compound Structure MOR
Binding		 DOR
Binding		 KOR
Binding		 MOR EC50 c, nM (% Stimulation) DOR EC50 c, nM
(% Stimulation)		 KOR EC50 c, nM
(% Stimulation)
Group 1. N-Cyanoalkyl Compounds and Compounds Lacking Substituents on the Aromatic Ring
1a graphic file with name molecules-25-02640-i001.jpg 4.51 ± 0.27 141 ± 2.8 90.3 ± 6.6 425 ± 133
(47.1 ± 3.3)		 NT NT
1b graphic file with name molecules-25-02640-i002.jpg 4.25 ± 0.29 72.2 ± 1.2 2.71 ± 0.22 DNS NT 24.3 ± 5.0
(89.6 ± 0.9)
1c graphic file with name molecules-25-02640-i003.jpg 90.5 ± 11.0 NT NT NT NT NT
1d graphic file with name molecules-25-02640-i004.jpg 40.1 ± 5.9 844 ± 107 NT NT NT NT
Group 2. Nitro Substituents
2a graphic file with name molecules-25-02640-i005.jpg 0.52 ± 0.01 6.07 ± 0.86 56.0 ± 8.2 1.9 ± 0.5
(26.6 ± 1.4)		 227 ± 53
(64.3 ± 3.3)		 NT
2b graphic file with name molecules-25-02640-i006.jpg 5.88 ± 0.38 92.5 ± 7.3 65.4 ± 7.7 DNS NT NT
Group 3. Alkyl and Alkoxy Substituents
2c graphic file with name molecules-25-02640-i007.jpg 0.86 ± 0.12 6.34 ± 0.65 44.0 ± 3.8 1.9 ± 0.7
(55.6 ± 2.1)		 23.1 ± 6.9
(95.4 ± 3.8)		 38.1 ± 10.6
(31.4 ± 4.2)
2d graphic file with name molecules-25-02640-i008.jpg 0.67 ± 0.05 5.43 ± 0.47 26.3 ± 1.9 DNS 33.6 ± 6.4
(48.9 ± 3.2)		 5.9 ± 1.7
(21.8 ± 0.8)
Group 4. Halides and Trifluromethyl Substituents
2e graphic file with name molecules-25-02640-i009.jpg 0.87 ± 0.10 13.4 ± 0.9 44.3 ± 6.0 2.5 ± 0.3
(42.6 ± 2.9)		 64.2 ± 9.9
(243 ± 49)		 DNS
2f graphic file with name molecules-25-02640-i010.jpg 0.49 ± 0.07 4.48 ± 0.43 30.2 ± 2.3 2.4 ± 0.3
(56.8 ± 7.5)		 54.1 ± 4.7
(86.7 ± 8.0)		 DNS
2g graphic file with name molecules-25-02640-i011.jpg 0.32 ± 0.04 3.57 ± 0.49 23.2 ± 2.8 2.1 ± 0.7
(100 ± 0.3)		 92.7 ± 17.0
(83.0 ± 3.3)		 DNS
2h graphic file with name molecules-25-02640-i012.jpg 2.70 ± 0.17 16.4 ± 0.4 NT 3.4 ± 1.2
(72.2 ± 5.5)		 35.7 ± 12.3
(82.3 ± 2.3)		 NT
2i graphic file with name molecules-25-02640-i013.jpg 1.09 ± 0.06 7.89 ± 1.10 NT 2.0 ± 1.0
(39.0 ± 2.1)		 2.4 ± 0.7
(83.8 ± 3.7)		 NT
Standard
- Morphine 3.26 ± 0.39 NT 145 ± 15 194 ± 21
(57 ± 5) [31]		 NT NT

a Binding assays were typically conducted in at least three independent experiments, each performed with triplicate observations using whole rat brains excluding cerebellum; Ki ± SEM (nM); NT = not tested—inactive (<50% activity at 100 nM concentration in exploratory binding assays (displaced less than half of radioligand). Also, compounds with low binding affinity (>50 nM) were not further examined in functional assays); b [35S]GTPγS functional assays: % stimulation compared to standard maximal at each receptor MOR = DAMGO; DOR = DPDPE; KOR = U69593) in C6 cells expressing MOR or DOR or CHO cells expressing KOR. All experiments were repeated on three separate occasions in duplicate. Values are given as means ± SEM; DNS = no stimulation (indicates antagonist activity when coupled with high receptor binding affinity); c EC50 = Effective dose for 50% maximal response.